bromochloroacetic-acid and Ichthyosis

Hereditary ichthyoses are due to mutations on one or both alleles of more than 30 different genes, mainly expressed in the upper epidermis. Syndromic as well as nonsyndromic forms of ichthyosis exist. Irrespective of etiology, virtually all types of ichthyosis exhibit a defective epidermal barrier that constitutes the driving force for hyperkeratosis, skin scaling, and inflammation. In nonsyndromic forms, these features are most evident in severe autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis, but to some extent also occur in the common type of non-congenital ichthyosis. A correct diagnosis of ichthyosis-essential not only for genetic counseling but also for adequate patient information about prognosis and therapeutic options-is becoming increasingly feasible thanks to recent progress in genetic knowledge and DNA sequencing methods. This paper reviews the most important aspects of nonsyndromic ichthyoses, focusing on new knowledge about the pathophysiology of the disorders, which will hopefully lead to novel ideas about therapy.

Topics: Administration, Cutaneous; Administration, Oral; Dermatologic Agents; Genetic Counseling; Genetic Testing; Genetic Therapy; Humans; Ichthyosis; Keratins; Microscopy; Mutation; Permeability; Retinoids; Skin; Skin Transplantation

A 5-year-old boy presented with widespread asymptomatic hyperpigmented verrucous plaques since 3 months of age. The lesions were distributed in a linear manner along Blaschko's lines on trunk and extremities and were accentuated in flexures and around joints. There was no history of blistering or redness and no other family member was affected. Ichthyosis hystrix (of Curth and Macklin) and generalized linear/mosaic epidermolytic hyperkeratosis (EHK) were considered in the differential diagnosis. Biopsy from both trunk lesion and lesion on knee revealed characteristic epidermolytic hyperkeratosis, thereby clinching the diagnosis of systematized linear EHK.

Topics: Child, Preschool; Dermatitis, Seborrheic; Diagnosis, Differential; Genes, Dominant; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins; Male

In the last few years the progresses in molecular analysis allow better definitions of ichthyoses and lead to the necessity of a new classification and a review of nomenclature of inherited ichthyoses. So, in 2007 the First Consensus Conference on Ichthyoses was performed. We present here a short review of the new classification of syndromic ichthyoses together with clinical and molecular features.

Topics: Humans; Ichthyosis; Keratins; Syndrome

Topics: Cations; Connexin 26; Connexins; Deafness; Genes, Recessive; Humans; Ichthyosis; Ion Transport; Keratinocytes; Keratins; Keratitis; Keratoderma, Palmoplantar; Keratoderma, Palmoplantar, Diffuse; Mosaicism; Nevus; Porokeratosis; Skin Diseases, Genetic; Sweat Gland Neoplasms; TRPV Cation Channels

The unfolded protein response (UPR) is a signaling pathway from the endoplasmic reticulum (ER) to the nucleus that protects cells from stress caused by misfolded or unfolded proteins. As such, ER stress is an ongoing challenge for all cells, given the central biologic importance of secretion as part of normal physiologic functions. Mild UPR is activated by mild ER stress, which occurs under normal conditions. Abnormal UPR is activated by severe ER stress, which occurs under pathological conditions. Abnormal UPR activation is associated with a number of diseases, including diabetes mellitus and Alzheimer's disease. Within skin tissues, keratinocytes in the epidermis are especially dependent upon a mild UPR for normal differentiation in the course of their differentiation into secretory cells in the uppermost granular layers. Association between abnormal UPR activation and hereditary keratoses, including Darier's disease, keratosis linearis with ichthyosis congenita and keratoderma syndrome, erythrokeratoderma variabilis, and ichthyosis follicularis with atrichia and photophobia syndrome, have been elucidated recently. This review describes the UPR in normal and abnormal keratinization and discusses the regulation of abnormal UPR activation by chemical chaperones as a potential treatment for one of the hereditary keratoses.

Topics: Animals; Cell Differentiation; Darier Disease; Endoplasmic Reticulum Stress; Gene Deletion; Humans; Ichthyosis; Keratinocytes; Keratins; Molecular Chaperones; Mutation; Photophobia; Protein Folding; Signal Transduction; Skin Diseases, Genetic; Unfolded Protein Response

Topics: Animals; Dermatitis, Seborrheic; Desmosomes; Epidermis; Genes, Dominant; Genes, Recessive; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Ichthyosis Bullosa of Siemens; Ichthyosis Vulgaris; Infant, Newborn; Keratinocytes; Keratins; Membrane Proteins; Mice; Mutation

Ichthyosis includes a number of subtypes from congenital severe forms, such as harlequin ichthyosis (HI), to mild non-congenital forms, such as ichthyosis vulgaris. Recently, research into the pathomechanisms of ichthyoses has dramatically advanced and led to the identification of several causative genes and molecules underlying the genetic defects. In most types of ichthyosis, pathogenic mechanisms are associated with defects in skin barrier function. Three major components of the stratum corneum barrier are (i) intercellular lipid layers, (ii) cornified cell envelope and (iii) keratin-filaggrin degradation products. The causative molecules underlying ichthyosis subtypes include ABCA12, lipoxygenase-3, 12R-lipoxygenase, CYP4F2 homolog, ichthyin and steroid sulphatase and all these are thought to be related to the intercellular lipid layers. Transglutaminase 1 has a function in cornified cell envelope formation. Keratins 1, 10 and 2 are involved in the keratin network of suprabasal keratinocytes and filaggrin are essential for formation of keratohyalin granules. In fact, loss of ABCA12 function leads to a defective lipid barrier in the stratum corneum, resulting in the HI phenotype and ABCA12 is a known keratinocyte lipid transporter associated with lipid transport in lamellar granules. Filaggrin gene mutations in ichthyosis vulgaris cause keratohyalin granule deficiency. Information concerning genetic defects and ichthyotic disease pathomechanisms are beneficial to develop effective therapy and provide information for genetic counselling including prenatal diagnosis for families affected by ichthyotic disease.

Topics: Animals; ATP-Binding Cassette Transporters; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Female; Filaggrin Proteins; Humans; Ichthyosis; Intermediate Filament Proteins; Keratins; Lipoxygenase; Mutation; Pregnancy; Prenatal Diagnosis; Receptors, Cell Surface; Skin; Skin Physiological Phenomena; Steryl-Sulfatase; Transglutaminases

Topics: Epithelium; Humans; Ichthyosis; Keratinocytes; Keratins; Prognosis; Skin

Ichthyosis bullosa of Siemens (IBS, MIM 146800) is a unique congenital ichthyosis characterized by mild epidermal hyperkeratosis over flexural areas, blister formation and the development of superficially denuded areas of hyperkeratotic skin. It is clinically difficult to distinguish severe IBS from mild bullous congenital ichthyosiform erythroderma (BCIE, MIM 113800). In the current literature, 19 IBS families with keratin 2e (K2e) mutations have been reported, despite only five IBS families having been reported before the first identification of K2e mutation in 1994. We studied four patients from three Japanese IBS families. They had previously been misdiagnosed as having BCIE before the correct diagnosis was made after mutation detection. To detect the pathogenic mutations, we performed direct sequencing of the entire coding regions of KRT2E encoding K2e in the patients and healthy family members. K2e mutations, a 1469T-->C transition (L490P) and a 1477G-->A transition (E493K) within the conserved 2B helix termination motif of the rod domain were detected in the families and the definite diagnosis of IBS was made in the four cases. The present results indicate that IBS is not such a rare entity as was previously thought, and accurate diagnosis is now available by mutation analysis.

Topics: Adult; Child; Child, Preschool; Diagnosis, Differential; DNA Mutational Analysis; Female; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Japan; Keratin-2; Keratins; Male; Middle Aged; Pedigree; Skin; Syndrome

The ichthyoses are a large, clinically, genetically, and etiologically heterogeneous group of disorders of cornification due to abnormal differentiation and desquamation of the epidermis. Although they differ in clinical features, inheritance, and structural and biochemical abnormalities of the epidermis, they often pose a diagnostic challenge. For each of the 12 ichthyoses and related disorders described here, the major disease genes have been identified and genotype-phenotype correlation have begun to emerge. The molecular findings reveal the functional importance and interactions of many different epidermal proteins and metabolic pathways, including major structural proteins (keratins, loricrin), enzymes involved in lipid metabolism (transglutaminase 1, lipoxygenases, fatty aldehyde dehydrogenase, steroid sulfatase, glucocerebrosidase, Delta8-Delta7 sterol isomerase, 3beta-hydroxysteroid dehydrogenase), and protein catabolism (LEKTI), peroxisomal transport and processing (Peroxin 7 receptor, Phytanoyl-CoA hydroxylase) and DNA repair (proteins of the transcription repair complex). This review highlights the spectacular advances in the molecular genetics and biology of heritable ichthyoses over the past decade. It illustrates the power of molecular diagnostics for refining disease classification, providing prenatal diagnosis, improving genetic counseling, and clinical management.

Topics: DNA Repair; Enzymes; Genotype; Humans; Ichthyosis; Keratins; Lipid Metabolism; Membrane Proteins; Mutation; Phenotype

The association of keratin mutations with genetic skin fragility disorders is now one of the best-established examples of cytoskeleton disorders. It has served as a paradigm for many other diseases and has been highly informative for the study of intermediate filaments and their associated components, in helping to understand the functions of this large family of structural proteins. The keratin diseases have shown unequivocally that, at least in the case of the epidermal keratins, a major function of intermediate filaments is to provide physical resilience for epithelial cells. This review article reflects on the variety of phenotypes arising from mutations in keratins and the reasons for this variation.

Topics: Corneal Dystrophies, Hereditary; Cytoskeleton; Epidermolysis Bullosa Simplex; Hair; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratinocytes; Keratins; Keratoderma, Palmoplantar; Mutation; Nevus; Phenotype; Skin Diseases

Keratins are the type I and II intermediate filament proteins which form a cytoskeletal network within all epithelial cells. They are expressed in pairs in a tissue- and differentiation-specific fashion. Epidermolysis bullosa simplex (EBS) was the first human disorder to be associated with keratin mutations. The abnormal keratin filament aggregates observed in basal cell keratinocytes of some EBS patients are composed of keratins K5 and K14. Dominant mutations in the genes encoding these proteins were shown to disrupt the keratin filament cytoskeleton resulting in cells that are less resilient and blister with mild physical trauma. Identification of mutations in other keratin genes soon followed with attention focussed on disorders showing abnormal clumping of keratin filaments in specific cells. For example, in bullous congenital ichthyosiform erythroderma, clumping of filaments in the suprabasal cells led to the identification of mutations in the suprabasal keratins, K1 and K10. Mutations have now been identified in 18 keratins, all of which produce a fragile cell phenotype. These include ichthyosis bullosa of Siemens (K2e), epidermolytic palmoplantar keratoderma (K1, K9), pachyonychia congenita (K6a, K6b, K16, K17), white sponge nevus (K4, K13), Meesmann's corneal dystrophy (K3, K12), cryptogenic cirrhosis (K8, K18) and monilethrix (hHb6, hHb1).In general, these disorders are inherited as autosomal dominant traits and the mutations act in a dominant-negative manner. Therefore, treatment in the form of gene therapy is difficult, as the mutant gene needs to be inactivated. Ways of achieving this are actively being studied. Reliable mutation detection methods from genomic DNA are now available. This enables rapid screening of patients for keratin mutations. For some of the more severe phenotypes, prenatal diagnosis may be requested and this can now be performed from chorionic villus samples at an early stage of the pregnancy. This review article describes the discovery of, to date, mutations in 18 keratin genes associated with inherited human diseases.

Topics: Epidermolysis Bullosa Simplex; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins; Keratoderma, Palmoplantar; Skin Diseases, Genetic

We report a large family with ichthyosis bullosa of Siemens (IBS) including eight affected members spanning three generations. The classical features of the disease were consistently observed with blistering, superficial peeling of the skin, and localized lichenified hyperkeratosis mainly confined to the limbs. Phenotypic variation, however, was also observed with some individuals exhibiting unusual clinical features. Specifically, the index patient was erythrodermic at birth; she subsequently developed a widespread pustular eruption. Erythroderma is classically absent in IBS and pustulation is very unusual. She also had hypertrichosis of the limbs, as did an affected female first cousin. This has not previously been reported in IBS. Electron microscopy showed complex aggregates of keratin in the spinous and granular layers associated, in places, with remarkably little cell lysis. Sequencing of genomic DNA revealed a mutation (E493K) in keratin 2e. A review of the literature on IBS indicates that E493K is the most commonly reported mutation to date and might represent a mutational hotspot for this disease.

Topics: Adult; Child; Female; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Infant; Keratin-2; Keratins; Male; Microscopy, Electron; Middle Aged; Mutation, Missense; Pedigree

There have been a number of major discoveries recently in the field of dermatological science which have enabled us to determine the causes of inherited skin diseases of previously unknown etiology. In this paper we will review some important aspects of the biology of epidermal differentiation and the recent advances in understanding of the molecular mechanism underlying genetic diseases of keratinization.

Topics: Epidermis; Humans; Ichthyosis; Keratins; Keratoderma, Palmoplantar; Keratosis

Genetic methods (both statistical and laboratory based), along with close clinical scrutiny, have led to the recent discovery that abnormal keratin genes underlie several disorders of cornification (Table 3). The ability to classify diseases based on the specific underlying gene mutation has now become a reality (e.g., the ability to distinguish IBS from EHK and to correlate palmoplantar hyperkeratosis in EHK with keratin 1 mutations vs. the lack of palmoplantar hyperkeratosis with keratin 10 mutations). Understanding how specific keratin mutations cause their associated clinical phenotypes will lead to better appreciation of the function of KIFs in epidermis in normal and disease states.

Topics: Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 17; Epidermolysis Bullosa Simplex; Genetic Linkage; Hamartoma; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins; Keratoderma, Palmoplantar; Mutation; Nail Diseases; Skin Diseases

Topics: Animals; Cell Differentiation; Cell Membrane; Humans; Ichthyosis; Ichthyosis, Lamellar; Intermediate Filaments; Keratinocytes; Keratins; Lipid Metabolism; Mutation; Transglutaminases

Epidermolytic hyperkeratosis is an autosomal dominant ichthyosis characterized by blistering, especially at birth and during childhood, and hyperkeratosis. Epidermolytic hyperkeratosis presents striking clinical heterogeneity, particularly between families. Several avenues of research have implicated an abnormality of epidermal differentiation in the pathogenesis of this disease. In a three-generation family with 20 affected individuals, we tested a variety of candidate loci and identified linkage to the type II keratin region on chromosome 12. Further investigation revealed a mutation in the H1 subdomain of the keratin 1 gene as the cause of EHK in this family. Because keratin 10 is the co-expressed partner of keratin 1, it was not surprising when abnormalities in keratin 10 were found in other families with EHK. We have examined 52 patients from 21 families and have identified at least six clinical phenotypes. The most useful distinguishing feature was the presence or absence of severe hyperkeratosis of the palms and soles. We and others are continuing to search for and characterize mutations in keratin 1 and 10 in patients with epidermolytic hyperkeratosis. Correlation of the clinical disease types with the specific mutations should lead to a better understanding of the relationship between keratin structure and function in normal and diseased epidermis.

Topics: Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins; Molecular Biology; Mutation

Harlequin ichthyosis is an inherited skin disorder that usually results in death shortly after birth. Although the clinical features of this disorder are well described, the underlying molecular basis is not understood. In this article, we discuss the results of the latest histologic, immunochemical, and Western immunoblotting studies done in our laboratory and propose a hypothesis for molecular basis of this disorder.. Previous experiments done in our laboratory show suggestive evidence for defective lipid synthesis and protein dephosphorylation in harlequin ichthyosis. Our latest study shows that the catalytic subunit of one of the most prevalent protein phosphatase, type 2A protein phosphatase, appears to be altered in some cases of type 2 harlequin ichthyosis.. Based on these observations and the known functions of protein phosphatase in keratinocytes, we hypothesize that the underlying molecular basis of harlequin ichthyosis may be related to mutations affecting protein dephosphorylation. We further describe approaches by which this hypothesis can be tested.

Topics: Cells, Cultured; Humans; Ichthyosis; Ichthyosis, Lamellar; Infant, Newborn; Keratinocytes; Keratins; Keratosis; Molecular Biology; Mutation; Phosphoprotein Phosphatases; Skin

Topics: Cell Differentiation; Cell Membrane; Chemical Phenomena; Chemistry; Epidermal Cells; Epidermis; Humans; Ichthyosis; Keratins; Keratosis; Lipid Metabolism

Topics: Acne Vulgaris; Adolescent; Child; Child, Preschool; Darier Disease; Etretinate; Female; Humans; Ichthyosis; Infant; Isomerism; Isotretinoin; Keratins; Keratoderma, Palmoplantar; Male; Pityriasis Rubra Pilaris; Psoriasis; Skin Diseases; Skin Diseases, Vesiculobullous; Tretinoin

Disturbances in the process of normal cornification leading to pathologic scaling provide the pathophysiologic basis for the ichthyoses. These disturbances may result from either abnormalities in protein metabolism (keratinization) (i.e., the "bricks") or in lipid metabolism (i.e., the "mortar") (Fig. 1). The evidence linking the various ichthyoses to defects in protein or lipid metabolism have been reviewed. It is likely that future advances will lead not only to a more complete understanding of the pathogenesis of these disorders, but also will shed significant light on the normal stratum corneum functions of barrier formation and desquamation, as well as lead the way to more rational and effective therapies. In recent years, prenatal diagnosis has been successfully performed in several of the ichthyoses. It is likely that improvements in our ability to prenatally diagnose those disorders will advance hand-in-hand with further progress in unraveling their underlying causes.

Topics: Animals; Cholesterol Esters; Epidermis; Fatty Acids, Essential; Female; Fetal Diseases; Humans; Ichthyosis; Keratins; Lipidoses; Mice; Pregnancy; Prenatal Diagnosis; Refsum Disease; Steryl-Sulfatase; Sulfatases; Syndrome; X Chromosome

Topics: Acrodermatitis; Amino Acid Metabolism, Inborn Errors; Basal Cell Nevus Syndrome; Epidermolysis Bullosa; Hair Diseases; Humans; Ichthyosis; Keratins; Keratosis; Neurofibromatosis 1; Psoriasis; Refsum Disease; Skin; Skin Diseases; Skin Neoplasms; Tuberous Sclerosis; Tyrosine; Warts; Xeroderma Pigmentosum

Topics: Animals; Carboxy-Lyases; Deoxyribonucleases; Estriol; Fetus; gamma-Glutamyltransferase; Hair; Humans; Ichthyosis; Keratins; Male; Ornithine Decarboxylase; Rats; Skin; Skin Neoplasms; Sulfatases

Topics: Fatty Acids; Fatty Acids, Essential; Humans; Hydrocarbons; Ichthyosis; Keratins; Lipid Metabolism; Lipids; Phospholipids; Psoriasis; Skin; Skin Diseases; Skin Physiological Phenomena; Sphingolipids; Sterols; Subcellular Fractions; Waxes

Topics: Animals; Fatty Acids, Essential; Female; Humans; Ichthyosis; Keratins; Male; Mice; Phytanic Acid; Skin

Topics: Animals; Cell Communication; Cell Differentiation; Cell Division; Cells, Cultured; Chick Embryo; Ectoderm; Epidermal Cells; Epidermis; Humans; Ichthyosis; Keratins; Mutation; Psoriasis; Skin Abnormalities

Topics: Cell Membrane; Cytoplasmic Granules; Humans; Ichthyosis; Keratins; Nevus; Organoids; Skin Diseases, Vesiculobullous; Skin Neoplasms; Vacuoles

Topics: Amino Acids; Animals; Chemical Phenomena; Chemistry; Collagen; Feathers; Glycine; Guinea Pigs; Hair; Histocytochemistry; Humans; Hydroxyproline; Ichthyosis; Keratins; Macromolecular Substances; Microscopy, Electron; Molecular Biology; Molecular Conformation; Molecular Weight; Nails; Sheep; Skin; Solubility; X-Ray Diffraction

Topics: Cholesterol; Eczema; Fatty Acids; Fatty Acids, Essential; Humans; Ichthyosis; Keratins; Lipoproteins; Psoriasis; Refsum Disease; Skin; Sterols

Liarozole, a novel imidazole derivative, inhibits the cytochrome P450-dependent 4-hydroxylation of retinoic acid, resulting in increased tissue levels of retinoic acid. Twelve male patients with ichthyosis were given oral liarozole, 150 mg twice daily, in an open study for 12 weeks. Immunohistochemical parameters of inflammation, epidermal proliferation and differentiation were assessed before and after treatment. Extent and severity of the skin lesions was markedly reduced in all patients. Clinical side-effects were reminiscent of those with synthetic retinoids. No relevant changes were found in the haematological, urinary and biochemical parameters. Immunohistochemical assessment showed a statistically significant induction of keratin 4 after liarozole treatment in 10 of 12 patients. In two of these patients keratin 13 was induced. This open study showed that oral liarozole treatment was efficacious and well tolerated in the treatment of different types of ichthyosis. The immunohistochemical results suggest a retinoid mechanism as the mode of action.

Topics: Adolescent; Adult; Aged; Androgen Antagonists; Cytochrome P-450 Enzyme Inhibitors; Follow-Up Studies; Humans; Ichthyosis; Imidazoles; Keratins; Male; Middle Aged; Prospective Studies; Severity of Illness Index

Topics: Humans; Ichthyosis; Keratins; Signal Transduction; Skin Neoplasms; Toll-Like Receptor 2

A 3-months old Chinese shar-pei puppy with ichthyosis was investigated. The dog showed generalized scaling, alopecia and footpad lesions. Histopathological examinations demonstrated a non-epidermolytic hyperkeratosis. The parents of the affected puppy did not show any skin lesions. A trio whole genome sequencing analysis identified a heterozygous de novo 3 bp deletion in the KRT1 gene in the affected dog. This variant, NM_001003392.1:c.567_569del, is predicted to delete a single asparagine from the conserved coil 1A motif within the rod domain of KRT1, NP_001003392.1:p.(Asn190del). Immunohistochemistry demonstrated normal levels of KRT1 expression in the epidermis and follicular epithelia. This might indicate that the variant possibly interferes with keratin dimerization or another function of KRT1. Missense variants affecting the homologous asparagine residue of the human KRT1 cause epidermolytic hyperkeratosis. Histologically, the investigated Chinese shar-pei showed a non-epidermolytic ichthyosis. The finding of a de novo variant in an excellent functional candidate gene strongly suggests that KRT1:p.Asn190del caused the ichthyosis phenotype in the affected Chinese shar-pei. To the best of our knowledge, this is the first description of a KRT1-related non-epidermolytic ichthyosis in domestic animals.

Topics: Animals; Asparagine; China; Dogs; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Infant; Keratin-1; Keratin-10; Keratins; Mutation

Topics: Acantholysis; Aged; Female; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins

Autosomal recessive congenital ichthyosis (ARCI) is a group of disorders characterized by abnormal desquamation of the skin and a disrupted epidermal water barrier. Ichthyin/NIPAL4 gene mutations have been identified in a subgroup of ARCI patients, but the role of ichthyin in epidermis remains elusive. In order to obtain new insights concerning the characteristics of ichthyin and the ARCI pathogenesis, we studied the expression and localization of ichthyin and related epidermal components in cultured keratinocytes and skin sections from patients with Ichthyin mutations and healthy controls. We observed an up-regulation of Ichthyin mRNA levels after in vitro differentiation of keratinocytes from both a patient with Ichthyin mutations and controls. Confocal and electron microscopy analyses of immunolabeled skin sections revealed that ichthyin localizes to desmosomes and keratins in both patients with mutant Ichthyin and controls, with an increased immunolabeling in patients. Nile red lipid analysis of skin sections exposed intra-cellular lipid accumulations in cells of the granular and cornified layers in patients but not in controls, consistent with the pathognomonic lipid membrane structures previously identified in epidermis from patients. Our combined findings indicate that ichthyin is associated with keratins and desmosomes in epidermis and is involved in lipid metabolism, possibly through processing of lamellar bodies. These results provide new clues to the understanding of the epidermal water barrier and the pathogenesis in ARCI.

Topics: Desmosomes; Epidermal Cells; Epidermis; Humans; Ichthyosis; Keratinocytes; Keratins; Lipid Metabolism; Membrane Lipids; Mutation; Receptors, Cell Surface; RNA, Messenger; Skin

Topics: Adult; Child; Diagnosis, Differential; Female; Humans; Ichthyosis; Keratins; Male; Permeability; Skin

Topics: Adult; Humans; Ichthyosis; Keratins; Male; Syndrome

Squamous metaplasia of endometrium is mostly manifested by morules or nodules of benign nonkeratinizing squamous cells intimately mixed with benign or malignant endometrial glands. It has been described with low-grade adenocarcinoma of the endometrium, as well as with various benign conditions, including hyperplasia, chronic endometritis, and endometrial polyps. However, extensive plaquelike, keratinizing squamous change is distinctly uncommon. To our knowledge, we describe the first case of extensive benign squamous keratinization with underlying endometrial adenocarcinoma.

Topics: Adenocarcinoma; Aged; Endometrial Neoplasms; Female; Gynecologic Surgical Procedures; Humans; Ichthyosis; Keratins; Uterus

In human skin, the 27-kd heat shock protein (hsp27), a member of the small hsp family, is expressed mainly in the upper epidermal layers. Hsp27 functions as a molecular chaperone and is involved in the regulation of cell growth and differentiation. According to experimental evidence, epidermal hsp27, through its chaperone function, might play a role in the assembly of keratin filaments and the cornified cell envelope. This study was conducted to assess the expression pattern of hsp27 in a panel of different ichthyoses. Twelve hereditary and acquired skin diseases associated with an ichthyotic phenotype and 2 corresponding mouse models were investigated by immunohistochemistry on formalin-fixed paraffin-embedded tissue, using a monoclonal antibody specific for hsp27. In ichthyosis vulgaris, lamellar ichthyosis, Sjögren-Larsson syndrome, Netherton syndrome, and acquired ichthyosiform skin condition, the pattern of hsp27 expression resembles healthy human skin. Hsp27 expression was reduced in bullous ichthyosiform erythroderma and annular epidermolytic ichthyosis, and absent in X-linked recessive ichthyosis (1/3 patients) and congenital hemidysplasia with ichthyosiform nevus and limb defects syndrome (1/1). In X-linked dominant chondrodysplasia, 3 small samples are completely negative and 2 larger samples show a pattern resembling random X inactivation. In the mouse models, tattered and bare patches, representing the murine analogues to X-linked dominant chondrodysplasia and congenital hemidysplasia with ichthyosiform nevus and limb defects syndrome, expression of hsp25 (the murine homologue of hsp27) also showed lyonization, demonstrating a clear-cut link between hsp27 expression and underlying molecular pathology. Our results show that loss of hsp27 is a rare event in human epidermis that is associated with specific genetic defects. Among the cases described here, these defects are either in suprabasal keratins or in enzymes involved in cholesterol biosynthesis. The expression and chaperone function of hsp27 might be modified by low/absent epidermal cholesterol and aberrant substrates (ie, keratins) resulting in protein misfolding, dyskeratosis, and thus contribute to the ichthyotic phenotype.

Topics: Animals; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Humans; Ichthyosis; Immunohistochemistry; Keratins; Mice; Molecular Chaperones; Neoplasm Proteins

Topics: Humans; Ichthyosis; Keratins; Mutation

A new variant of congenital exfoliative ichthyosis in two related Bedouin families is reported. The ichthyosis appeared shortly after birth as a fine peeling of nonerythematous skin on the palms and soles. The prominent well-demarcated areas of denuded skin in moist and traumatized regions resembled the 'mauserung' phenomenon of ichthyosis bullosa of Siemens (IBS). Unlike in IBS, epidermolysis is absent on histological examination. Electron microscopy revealed a prominent intercellular oedema and numerous aggregates of keratin filaments in basal keratinocytes. Abnormal keratin (K) 1 expression was seen in the affected epidermis; however, all other keratins, including K2e, had a distribution comparable to that seen in normal controls. A maximum two-point LOD score of 2.53 and multipoint LOD score of 3.76 were obtained for marker D12S390, suggesting linkage to the type II keratin cluster on chromosome 12q13. Sequencing of both the K1 gene, the promotor and the 3' calcium regulatory region did not reveal a mutation. K2e and K5 genes, as well as the genes harboured within the minimal region, such as retinoic acid receptor gamma, sterol O-acyltransferase 2, integrin beta7 and insulin-like growth factor binding protein-6, were also excluded. This combination of clinical, histological, ultrastructural and genetic features has not been previously reported in other congenital exfoliative ichthyoses. We therefore suggest that it represents a new form of exfoliative ichthyosis.

Topics: Adolescent; Child, Preschool; Chromosomes, Human, Pair 12; Diseases in Twins; Female; Genes, Recessive; Genetic Linkage; Humans; Ichthyosis; Infant; Keratinocytes; Keratins; Lod Score; Male; Microscopy, Electron; Pedigree

Unraveling the molecular basis of inherited disorders of epithelial fragility has led to understanding of the complex structure and function of keratin intermediate filaments. Keratins are organized as a central alpha-helical rod domain flanked by nonhelical, variable end domains. Pathogenic mutations in 19 different keratin genes have been identified in sequences corresponding to conserved regions at the beginning and end of the rod. These areas have been recognized as zones of overlap between aligned keratin proteins and are thought to be crucial for proper assembly of keratin intermediate filaments. Consequently, all keratin disorders of skin, hair, nail, and mucous membranes caused by mutations in rod domain sequences are characterized by perinuclear clumping of fragmented keratin intermediate filaments, thus compromising mechanical strength and cell integrity. We report here the first mutation in a keratin gene (KRT1) that affects the variable tail domain (V2) and results in a profoundly different abnormality of the cytoskeletal architecture leading to a severe form of epidermal hyperkeratosis known as ichthyosis hystrix Curth-Macklin. Structural analyses disclosed a failure in keratin intermediate filament bundling, retraction of the cytoskeleton from the nucleus, and failed translocation of loricrin to the desmosomal plaques. These data provide the first in vivo evidence for the crucial role of a keratin tail domain in supramolecular keratin intermediate filament organization and barrier formation.

Topics: Amino Acid Sequence; Base Sequence; Cytoplasm; Frameshift Mutation; Heterozygote; Humans; Ichthyosis; Intermediate Filaments; Keratins; Keratoderma, Palmoplantar; Membrane Proteins; Microscopy, Electron; Molecular Sequence Data; Pedigree; Protein Isoforms; Protein Structure, Tertiary; Tissue Distribution

Ichthyosis bullosa of Siemens is a unique type of congenital ichthyosis characterized by mild hyperkeratosis over the flexural areas and blister formation after mechanical trauma and superficial denuded areas in the hyperkeratotic skin. Recently, mutations in the helix initiation or termination motifs of keratin 2e (KRT2E) have been described in ichthyosis bullosa of Siemens patients. The majority of the mutations reported to date lie in the 2B region. We report a novel amino acid substitution mutation (asparagine-->aspartic acid) in codon 192 at the conserved 1A helix initiation site of the rod domain of KRT2E in a Japanese family with ichthyosis bullosa of Siemens. Our data indicate aspartic acid substitution in codon 192 in the 1A helix initiation site is deleterious to keratin filament network integrity and leads to ichthyosis bullosa of Siemens phenotype.

Topics: Amino Acid Sequence; Amino Acid Substitution; Asian People; Base Sequence; Female; Humans; Ichthyosis; Japan; Keratin-2; Keratins; Middle Aged; Molecular Sequence Data; Mutation; Pedigree; Skin Diseases, Vesiculobullous

Ichthyosis bullosa of Siemens (IBS) is a rare disorder of cornification characterized by blister formation in the upper suprabasal layers of the epidermis. Molecular analysis of IBS has identified mutations in the keratin 2e (K2e) gene, which is located in the type II keratin gene cluster on chromosome 12q. We have studied two IBS families and have identified heterozygous point mutations in codon 493 of the K2e gene in both families. Whereas a non-conservative amino acid substitution at position 117 of the 2B region of K2e (E117K) was associated with a severe phenotype in family 1, family 2 showed mild clinical features as a result of a conservative substitution (E117D). These data suggest a phenotype-genotype correlation in these families.

Topics: Adult; Alleles; Amino Acid Sequence; Amino Acid Substitution; Base Sequence; DNA; DNA Primers; Female; Genotype; Heterozygote; Humans; Ichthyosis; Keratin-2; Keratins; Male; Pedigree; Phenotype; Point Mutation; Polymerase Chain Reaction

Ichthyosis bullosa of Siemens (IBS; MIM: 146800) is an autosomal dominant disorder of keratinization characterized by epidermolytic hyperkeratosis without erythroderma. The clinical features are less marked than those of bullous congenital ichthyosiform erythroderma with relatively mild hyperkeratosis usually limited to the skin flexures. Mutations in the epithelial cytokeratin 2e (K2e), which is expressed in a differentiation-specific fashion in the upper spinous and granular layers of the epidermis, have been shown to cause IBS. We detected a novel mutation in a three generation kindred with IBS (1448T-->A) within exon 7 of the KRT2E gene. This is predictive of an I483N substitution in the 2B domain of K2e. This extends the range of mutations reported to date and illustrates the usefulness of molecular genetics in the diagnosis of this disorder.

Topics: DNA Mutational Analysis; Humans; Ichthyosis; Keratin-2; Keratins; Mutation, Missense; Pedigree; Polymerase Chain Reaction; Skin Diseases, Vesiculobullous

Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin disorder with clinical features similar to epidermolytic hyperkeratosis (EHK). Both diseases have been linked to the type II keratin cluster on chromosome 12q. Hyperkeratosis and blister formation are relatively mild in IBS compared with EHK, and the lysis of keratinocytes is restricted to the upper spinous and granular layers of the epidermis of IBS patients, whereas in EHK lysis occurs in the lower spinous layer. Recently, mutations in the helix initiation and termination motifs of keratin 2e (K2e) have been described in IBS patients. The majority of the mutations reported to date lie in the 2B region. In this report, we have examined a large kindred in which the disease was originally diagnosed as EHK and mapped to the type II keratin cluster on chromosome 12q. Molecular analysis revealed a novel amino acid substitution at the beginning of the conserved 1A region of the rod domain (I4N) of K2e, resulting from a T to A transversion in codon 188.

Topics: Amino Acid Sequence; Base Sequence; DNA Mutational Analysis; Female; Humans; Ichthyosis; Keratin-2; Keratins; Male; Mutation; Pedigree; Skin Diseases, Vesiculobullous

Harlequin ichthyosis (HI) is a severe congenital ichthyosis in which newborn infants are covered with a thick plate of stratum corneum. We examined skin specimens from a variety of regions of the body including the scalp, face, tongue, trunk, upper and lower extremities, digits, palms, and soles of three fetuses affected with HI that were diagnosed prenatally. In all the skin regions, characteristic morphological abnormalities (absent or abnormal lamellar granules and intercellular lamellae, lipid inclusions in the cornified cells) were expressed in the late second trimester of the fetal period. The cornified cells in hair canals showed morphological abnormalities of HI more strongly than the interfollicular epidermis. Immunoblot study of epidermal extracts revealed that profilaggrin was much more prominent than filaggrin in all the hairy skin regions where the hair canals were extensively keratinized, but filaggrin was prominent in the palm. These observations support the idea that, in the hairy skin, HI phenotype expression is associated with keratinization and abnormal filaggrin metabolism in hair. In addition, the prenatal diagnosis or prenatal exclusion of HI is thought to be possible from whichever site of the fetal body the skin biopsy is taken in the late second trimester of the fetal period.

Topics: Biopsy; Cytoplasmic Granules; Epidermis; Female; Filaggrin Proteins; Gestational Age; Humans; Ichthyosis; Immunoblotting; Immunohistochemistry; Infant, Newborn; Intermediate Filament Proteins; Keratins; Lipids; Microscopy, Electron; Pregnancy; Prenatal Diagnosis; Protein Precursors; Skin; Tissue Distribution

Inherited disorders of keratinization can result in a wide variety of clinical features. The skin is usually affected with blistering or ichthyosis, but other body systems may be involved. The severity of these disorders varies greatly. This article reviews the advances in the molecular pathology of these disorders, and shows how this has benefited our understanding of cell biology.

Topics: Epithelial Cells; Gene Expression; Genes; Humans; Ichthyosis; Keratinocytes; Keratins; Mutation; Phenotype

We and others have previously shown that ichthyosis bullosa of Siemens, an autosomal dominant disorder characterized by epidermal thickening and blistering, is caused by mutations in the late-differentiation keratin K2e. Here, we have determined the genomic organization and complete sequence of the KRT2E gene, which consists of nine exons, spanning 7634 bp of DNA. The gene was mapped by high-resolution radiation-hybrid mapping to the interval between microsatellite markers D12S368 and CHLC.GATA11B02.1112. Several intragenic polymorphisms were detected, including an 18 bp duplication in exon 1, corresponding to the V1 domain of the K2e polypeptide. Genomic polymerase chain reaction conditions were optimized for all exons, and two novel mutations, N192Y in the 1A domain and E482K in the 2B domain of K2e, were found in ichthyosis bullosa of Siemens families. Mutations were excluded from 50 normal unrelated individuals by restriction analysis. These results emphasize that mutations in K2e underlie ichthyosis bullosa of Siemens and provide a comprehensive mutation detection strategy for ongoing studies of keratinizing disorders.

Topics: Chromosome Mapping; Exons; Humans; Hybrid Cells; Ichthyosis; Introns; Keratin-2; Keratins; Mutation; Pedigree; Polymorphism, Genetic; Protein Structure, Tertiary; Sequence Analysis, DNA; United Kingdom

Ichthyosis bullosa of Siemens is a rare autosomal dominant skin disorder whose clinical findings are quite similar to those of epidermolytic hyperkeratosis. The differences between those two diseases include absence of erythroderma and different distributions in the skin in ichthyosis bullosa of Siemens. Recent studies have confirmed that ichthyosis bullosa of Siemens is caused by the mutation in the keratin 2e (K2e) gene, which is expressed in the upper spinous and granular layers. We have identified a sporadic case of ichthyosis bullosa of Siemens; based on diagnosis by histopathological findings, the K2e gene of the patient was analysed. Direct sequencing of PCR products revealed a single base change in sequences encoding the highly conserved end of the 2B rod domain segment of the K2e gene. This mutation results in substitution of the codon for glutamic acid by a codon for lysine in position 493 in K2e (E493K). Mutations of the K2e gene involving five different residue positions (Q187P, T485P, L490P, E493D, E493K and E494K) are known to cause ichthyosis bullosa of Siemens. Of these sites, E493, which is conserved in type I and type II keratin genes, is the most frequently altered amino acid in the K2e gene. These data together suggest that this codon constitutes a hot spot for mutations in the K2e gene.

Topics: Amino Acid Substitution; Base Sequence; Child, Preschool; Codon; Conserved Sequence; Epidermis; Exons; Glutamic Acid; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratin-2; Keratins; Lysine; Male; Microscopy, Electron; Point Mutation; Polymerase Chain Reaction; Sequence Analysis, DNA

Annular epidermolytic ichthyosis is a distinct phenotypic variant of bullous congenital ichthyosiform erythroderma that has recently been described in two separate kindreds. Individuals with this variant present with bullous ichthyosis in early childhood and hyperkeratotic lichenified plaques in the flexural areas and extensor surfaces at later ages. Characteristically, they also develop intermittent bouts of annular and polycyclic, erythematous, scaly plaques on the trunk and proximal extremities. We now describe a third kindred with annular epidermolytic ichthyosis. Molecular analysis of this family revealed a novel mutation resulting in an isoleucine to threonine substitution at residue 107 (codon 446) within the highly conserved helix termination motif at the end of the rod domain of keratin 10.

Topics: Adult; Base Sequence; Child; Female; Genetic Variation; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratin-10; Keratins; Male; Middle Aged; Mutation; Pedigree; Phenotype; Polymorphism, Restriction Fragment Length; Sequence Analysis

Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin condition with features similar to epidermolytic hyperkeratosis (EH). Clinical symptoms are characterized by mild hyperkeratosis with an acral distribution. Histology shows epidermolysis of upper spinous and granular cells, whereas ultrastructurally, tonofilaments form perinuclear aggregates. IBS has been linked to the type II keratin cluster on chromosome 12q, and K2e mutations have recently been identified in IBS patients. We have studied genomic DNA from two IBS families and in both cases heterozygous point mutations were found in the 2B helical domain of K2e. One family had an established mutation in codon 493 (E493K), whereas the other had an unreported mutation in the adjacent codon (E494K). Both mutations were confirmed by allele-specific PCR. These data reinforce the hypothesis that mutations in the TYRKLLEGEE motif of the 2B helix are deleterious to keratin filament network integrity and provide further evidence for the involvement of K2e mutations in IBS.

Topics: Adolescent; Base Sequence; Child, Preschool; Conserved Sequence; Exons; Female; Genes, Dominant; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins; Male; Point Mutation; Protein Conformation

We have previously reported 18 cases of an ichthyosiform contact dermatitis caused by antiseptic solutions containing 3% cetrimide and 0.3% chlorhexidine. The reaction was traced to cetrimide, a mixture of quaternary ammonium compounds that are widely used as disinfectants and detergents. Quaternary ammonium compounds are known irritants. To elucidate the pathogenesis of the abnormal keratinization caused by cetrimide, electron microscopy was performed on biopsied lesions from five patients and on specimens from rabbits in which a mild reaction had been induced by closed patch with Savlon, cetrimide, and chlorhexidine. The patients' samples revealed hyperkeratosis with striking vesiculation of lamellar bodies in the granular cells and upper spinous cells, premature secretion of lamellar bodies, and abundant remnants of lamellar bodies and retention of desmosomes between the corneocytes. Similar lamellar bodies changes were induced in rabbit skin after 48 hours of closed patch with Savlon 1:30 and cetrimide 0.1%, but not with chlorhexidine 3%-further indication that cetrimide was the cause of the dermatitis. We conclude that the abnormal keratinization can be attributed, at least in part, to dysfunction of lamellar bodies resulting from the direct effects of cetrimide on the lipids and enzymes of lamellar bodies. Vesiculation with dysfunction of lamellar bodies may be an important pathogenetic mechanism in irritant dermatitis caused by quaternary ammonium compounds.

Topics: Animals; Anti-Infective Agents, Local; Anti-Inflammatory Agents, Non-Steroidal; Blister; Cetrimonium; Cetrimonium Compounds; Chlorhexidine; Cytoplasmic Granules; Dermatitis, Contact; Dermatitis, Irritant; Desmosomes; Drug Combinations; Epidermis; Humans; Ichthyosis; Keratinocytes; Keratins; Keratosis; Lipid Metabolism; Microscopy, Electron; Organelles; Patch Tests; Rabbits; Skin

We report a novel mutation in a case of ichthyosis bullosa of Siemens that results in a threonine --> proline substitution in a novel location, codon 485 in a highly conserved residue position of the IATYRKLLEGE consensus motif at the end of the 2B rod domain segment of the keratin 2e chain. The disease phenotype is consistent with the inappropriate substitution of a proline near the end of the rod domain, because it lies near the predicted molecular overlap region of coiled-coil molecules, which is critical for the maintenance of the structural integrity of keratin intermediate filaments.

Topics: Biopsy; Exons; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins; Point Mutation; Proline; Protein Structure, Tertiary; Skin; Threonine

Long-term survivors of harlequin ichthyosis (HI) have raised a controversy over the differences between HI and lamellar ichthyosis (LI). Abnormal lamellar granules and the failure of conversion from profilaggrin to filaggrin have been reported in HI. On the other hand, malformation of the cornified cell envelope as a result of mutation of keratinocyte transglutaminase has been found in LI. In the present study, we analyzed the distribution of keratins, filaggrin/profilaggrin and cornified cell envelope proteins in the epidermis in HI. We studied a newborn Japanese male with typical clinical features of HI. Electron microscopic observation of a skin biopsy specimen taken from the trunk revealed the presence of lipid inclusions within the cornified cells, the absence of lamellar granules in the granular layer keratinocytes, and a lack of extracellular lamellar structures between the first cornified cell and the granular cell. Immunohistochemical labeling showed a normal distribution of keratins (keratins 1, 5, 10, and 14), filaggrin/profilaggrin and cornified cell envelope proteins (involucrin, small proline-rich proteins, and loricrin) in the epidermis of lesional skin. The present observations of the patient's skin verified that keratins and cornified cell envelope proteins are normally expressed in HI, thus demonstrating a different pathogenesis between HI and LI.

Topics: Epidermis; Filaggrin Proteins; Humans; Ichthyosis; Infant, Newborn; Intermediate Filament Proteins; Keratins; Male; Membrane Proteins; Protein Precursors; Skin

We report the case of a second patient with the extraordinary ultrastructural findings of vacuolated structures intermingled with membranes in the perinuclear part of the upper epidermal cells. Clinical, light microscopic, and electron microscopic features of this particular presentation of ichthyosis congenita type III have already been presented by K. M. Niemi and L. Kanerva in 1989. Although our patient has more or less the same light and electron microscopic findings, the clinical picture is more severe. The patient was born as a collodion baby. Later, he showed signs of generalized severe involvement with large scales, erythrodermia, and itching. Successful therapy with retinoids resulted in complete removal of the hyperkeratosis but left the striking reticulate skin pattern. Noting the heterogeneous clinical presentation, the specific electron microscopic findings are diagnostic. No biochemical data on this disease are known.

Topics: Adult; Cell Nucleus; Cytoplasmic Granules; Dermatitis, Exfoliative; Dermatologic Agents; Epidermis; Humans; Hyalin; Ichthyosis; Keratins; Keratosis; Male; Microscopy, Electron; Mitochondria; Pruritus; Retinoids; Skin; Vacuoles

Topics: Cell Nucleus; Child, Preschool; Cytoplasm; Gene Expression; Humans; Ichthyosis; Intermediate Filaments; Keratinocytes; Keratins; Male

Ichthyosis bullosa of Siemens (IBS) is a congenital bullous ichthyosis without erythroderma. In contrast to bullous congenital ichthyosiform erythroderma (BCIE), there is a relatively mild involvement of the skin and epidermolytic hyperkeratosis (EHK) is restricted to the upper suprabasal layers of the epidermis. Tonofilament aggregation was observed by EM in suprabasal cells from affected patients in the two families under study, indicative of a keratin abnormality. Keratin 2e is a differentiation specific type II keratin expressed suprabasally in the epidermis. Part of the K2e gene was amplified by polymerase chain reaction using genomic DNA from affected and unaffected individuals from two IBS families. Direct sequencing of polymerase chain reaction products revealed a point mutation in the highly conserved helix termination motif, producing the protein sequence change LLEGEE-LLEGKE. This mutation was found in all affected members of a five-generation kindred and also in a sporadic case in a second unrelated family. No mutation was seen in unaffected individuals. The mutation destroys a MnlI restriction site, which allowed exclusion of the mutation from a population of 50 unaffected unrelated individuals by restriction fragment analysis of K2e PCR products. This is the sixth keratin gene found to be involved in an inherited epidermal disorder.

Topics: Base Sequence; Child; Diagnosis, Differential; Female; Heterozygote; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Intermediate Filaments; Keratin-2; Keratins; Microscopy, Electron; Molecular Probes; Molecular Sequence Data; Pedigree; Point Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length

Ichthyosis bullosa of Siemens is an autosomal dominant disease characterized by mild hyperkeratosis and blistering. Autosomal dominant ichthyosis exfoliativa is a recently described disease with clinical features similar to ichthyosis bullosa of Siemens, but in contrast to ichthyosis bullosa of Siemens no histologic signs typical for epidermolytic hyperkeratosis are observed. We used linkage analysis to test whether keratin gene mutations might underlie both diseases. This analysis showed linkage of both disorders with the region of chromosome 12 in which the keratin type II gene cluster is located. The keratin type I gene cluster on chromosome 17 is excluded. These data, combined with clinical observations, strongly suggest that the genes coding for keratin 1 or keratin 2e, both expressed in the suprabasal compartment of the epidermis and located in the type II gene cluster, are candidate genes for ichthyosis bullosa of Siemens and ichthyosis exfoliativa.

Topics: Base Sequence; Genes, Dominant; Genetic Linkage; Genetic Markers; Humans; Ichthyosis; Keratin-2; Keratins; Molecular Probes; Molecular Sequence Data; Multigene Family; Pedigree

Topics: Humans; Hyperkeratosis, Epidermolytic; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Keratins; Keratoderma, Palmoplantar; Point Mutation

Ichthyosis bullosa of Siemens (IBS) is an autosomal dominant skin disorder that resembles epidermolytic hyperkeratosis (EHK). We have identified mutations in two families originally diagnosed with EHK and in four families diagnosed with IBS at the same codon in the highly conserved carboxy terminal of the rod domain of keratin 2e, thus revealing a mutational hot spot. Our results allow a differential diagnosis to be made between IBS and EHK at the genetic level and we suggest that patients diagnosed with EHK, but lacking keratin K1 or K10 mutations, should be re-examined for mutations in their K2e genes.

Topics: Adult; Amino Acid Sequence; Base Sequence; Diagnosis, Differential; DNA; DNA Primers; Female; Genes, Dominant; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratin-2; Keratins; Male; Molecular Sequence Data; Molecular Structure; Mutation; Pedigree

Ichthyosis hystrix Curth-Macklin is a rare autosomal dominant disease characterized clinically by hyperkeratosis and ultrastructurally by disruption of the keratin intermediate filament network of suprabasal keratinocytes. We have used linkage analysis to test whether a keratin gene mutation might underlie this disease. This analysis excluded the keratin gene loci as the sites for the disease-causing mutation in one affected kindred.

Topics: Chromosomes, Human, Pair 12; Family Health; Female; Humans; Ichthyosis; Keratins; Male; Mutation; Pedigree

Topics: Animals; Epidermis; Humans; Ichthyosis; Keratins; Mice

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare genetic disorder. The epidermal abnormalities associated with the unilateral ichthyosis have previously been examined only by morphology. In order to describe these abnormalities more completely we analyzed the expression of markers of epidermal differentiation (keratins and filaggrin), grew keratinocytes in culture, and correlated the results with ultrastructural features. Expression of all differentiation markers was significantly reduced or absent, whereas keratins K5 and K14 and keratins K6 and K16 were strongly expressed in lesional epidermis, suggesting that basal cell keratin expression was not down-regulated as in normal epidermis and that lesional keratinocytes mature via an abnormal pathway. When removed from the tissue and grown in culture, keratinocytes from lesional and non-lesional biopsies had similar phase microscopic morphology as well as keratin and profilaggrin expression, in contrast to the extreme differences in vivo. Lesional keratinocytes also had similar contents of keratin filaments and keratohyalin, but showed abnormal accumulation of intercellular vesicles and debris and altered cell-cell and cell-substratum interaction. Comparison of the results in tissue and in culture suggests that systemic or dermal factors influence the abnormal structural protein expression and ichthyosiform epidermal differentiation seen in CHILD syndrome, but that lesional keratinocytes maintain abnormalities in the secretion and accumulation of extracellular material in vitro similar to the lesional tissue in vivo.

Topics: Abnormalities, Multiple; Biopsy; Electrophoresis, Polyacrylamide Gel; Female; Filaggrin Proteins; Humans; Ichthyosis; Immunohistochemistry; Infant; Intermediate Filament Proteins; Keratins; Limb Deformities, Congenital; Skin; Skin Abnormalities; Syndrome

A 37-year-old woman developed ichthyosiform desquamation of the skin and a severe diffuse alopoecia 3 weeks after taking the antidepressant maprotilin. No signs of inflammation were present. Histology revealed acanthosis with preserved stratum granulosum, follicular hyperkeratosis and dystrophic changes of the hair follicle. Electron microscopy revealed rarefication of tonofilaments and necrobiotic changes of epidermal keratinocytes with vacuolar degeneration of the cytoplasm and disorganization of the organelles. Pathogenetically this disease represents a drug-induced transitory disorder to keratinization, which had resulted in desquamation of the stratum corneum and alopecia. The authors propose the designation corneolysis for this pathogenetic principle.

Topics: Adjustment Disorders; Adult; Alopecia; Female; Humans; Huntington Disease; Ichthyosis; Keratins; Maprotiline; Microscopy, Electron; Skin

The extracellular matrix glycoprotein tenascin is sparsely distributed in normal human dermis. The authors have shown that in a number of skin diseases (psoriasis, skin tumors), tenascin expression is strongly increased. In this immunohistochemical study, using polyclonal and monoclonal antisera, we have tested the hypothesis that tenascin expression in vivo is linked to epidermal proliferation. Using the sellotape stripping model in normal human skin, which causes a rapid recruitment of keratinocytes into the cell cycle, induction of tenascin expression was found in the upper dermis within 24 hours after stripping. In contrast, in normoproliferative monogenic disorders of keratinization (X-linked recessive ichthyosis, autosomal dominant ichthyosis vulgaris, non-erythrodermic lamellar ichthyosis), no increase in tenascin expression was found compared with normal skin. These findings demonstrate a relationship between epidermal proliferation and metabolic alterations in the dermal compartment.

Topics: Cell Adhesion Molecules, Neuronal; Cell Division; Epidermal Cells; Epidermis; Extracellular Matrix; Extracellular Matrix Proteins; Fibronectins; Gene Expression; Humans; Ichthyosis; Immune Sera; Immunohistochemistry; Keratinocytes; Keratins; Skin Diseases; Tenascin

Skin biopsies and scale samples from nine infants and one fetus affected with harlequin ichthyosis (HI) were obtained from eight families. Epidermal differentiation was examined by morphologic and biochemical criteria and cell culture studies. Two striking abnormalities were identified; first, keratin and filaggrin expression were abnormal and varied between cases, and, second, in all cases lamellar granules were absent or abnormal, and intercellular lamellae within the stratum corneum were absent. Three HI phenotypes were distinguished by variable expression of epidermal structural proteins. Cases were classified by the absence (type 1) or presence (types 2 and 3) of keratins K6 and K16 ("hyperproliferative" keratins) and by the presence of profilaggrin in the interfollicular epidermis (types 1 and 2 only). Profilaggrin is apparently not converted to filaggrin, but it is retained in the scale. The block in profilaggrin processing may be due to an inactive phosphatase. Siblings in two families (presenting with types 1 and 2) showed the same type classification suggesting that expression of the phenotype is consistent within families but differs between families. Cultured HI keratinocytes were normal by phase microscopy, but abnormal by electron microscopy with no lamellar granules and extensive stacking of the upper layers. We conclude that harlequin ichthyosis is a genetically heterogeneous group of disorders with altered lamellar granules, intercellular lipids, and variation in expression and/or processing of structural protein markers of normal epidermal keratinization. Furthermore, the lamellar granule and structural protein defects may be indirectly related via a mechanism involving phosphorylation/dephosphorylation.

Topics: Biopsy; Cells, Cultured; Cytoplasmic Granules; Fetus; Filaggrin Proteins; Humans; Ichthyosis; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Metabolism, Inborn Errors; Phosphoproteins; Protein Precursors; Proteins; Sweat Glands

The pathogenesis of a rare form of the ichthyotic diseases, ichthyosis hystrix Curth-Macklin, was investigated by immunohistochemistry and electron microscopy. Monoclonal antibodies (Mabs) against keratins expressed in normal basal cells (PKK2 and KA1), Mabs against keratins only present in normal fetal skin (PKK1), and Mabs against keratins 1, 2, 10, and 11 (KA5 and K8.60) were used. The Mabs reacting with normal basel cells showed an increased reaction with many cell layers. The Mab PKK1 distinctly reacted with the basal cell layer, suggesting an expression of fetal keratins. Electron microscopic study of both normal-looking and involved skin revealed the keratinization disorder characterized by tonofilament shells, perinuclear vacuoles, and binuclear keratinocytes. The results suggest that there is no prematurity of keratinization, but rather a pathological expression of specific keratin genes leading to expression of fetal keratins in this form of ichthyosis hystrix.

Topics: Adult; Child; Female; Humans; Ichthyosis; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Skin

Psoriasis occurring in a patient with lamellar ichthyosis is reported. Similar self-limited episodes had occurred earlier. On histopathologic examination of a biopsy specimen, an eruptive plaque showed parakeratosis and a reduction in the granular layer. Electrophoretic analysis of the keratins isolated from the epidermis of a plaque showed a reduction in the amount of the 67 kd polypeptide compared to the keratins of ichthyosis epidermis. Both of these findings support the diagnosis of psoriasis. Epilyt, applied daily, was effective in removing scales.

Topics: Adult; Biopsy; Dermatologic Agents; Female; Humans; Hyperplasia; Ichthyosis; Keratins; Psoriasis; Skin

Epidermal keratinocytes separated from skin lesions of non-bullous congenital ichthyosiform erythroderma were investigated in an attempt at experimental reproduction of this keratinization disorder. In vitro studies on growth and differentiation of pathological keratinocytes isolated from the influence of the host's dermal and humoral components were performed using the immersed epidermal cell culture technique. Ten to 25-day-old confluent and stratified cultures were examined by means of photonic and electron microscopy, and stained with various differentiation markers for indirect immunofluorescence studies. The cultured epidermis showed low-grade differentiation and no clear-cut evenly distributed signs of the original disease. Grafting on congenitally athymic nude mice allowed further differentiation of the epidermal sheets and re-expression of the histologic and ultrastructural features of non-bullous congenital ichthyosiform erythroderma. Thus, the purely epidermal origin of this particular form of autosomal recessive ichthyosis could be confirmed. Large amounts of pathological keratinocytes generated from small skin biopsies may be used for experimental purposes after grafting on several athymic animals.

Topics: Animals; Cell Differentiation; Cells, Cultured; Child; Child, Preschool; Epidermal Cells; Epidermis; Female; Fluorescent Antibody Technique; Humans; Ichthyosis; Keratins; Mice; Mice, Nude; Transplantation, Heterologous

In 30% to 40% of cases atopic dermatitis (AD) is believed to be associated with autosomal dominant ichthyosis vulgaris (ADI). The diagnosis of ADI can be proved by the ultrastructural demonstration of a defective keratohyalin (KH) synthesis, resulting in minute granules of crumbly appearance in only one layer of granular cells. To investigate the suggested frequent association of ADI with AD, ultrastructural examination of dry skin of 49 AD patients was performed. Only in 2 patients abnormal KH was demonstrated by electron microscopy. 17 patients, including the 2 patients with abnormal KH, showed hyperlinear palms. The present study shows that hyperlinear palms and dry skin are in most cases a phenotypic marker of AD alone and not a sign of concomitant ADI. A histologically one-layered or absent stratum granulosum may occur in the dry skin of patients with only AD and does not indicate a manifestation of concomitant ADI in all cases.

Topics: Adolescent; Adult; Dermatitis, Atopic; Female; Foot Dermatoses; Hand Dermatoses; Humans; Hyalin; Ichthyosis; Keratins; Male; Skin; Skin Diseases

The hereditary forms of ichthyosis can be considered to be models of impaired terminal epidermal differentiation. Analysis of the cytokeratin polypeptide pattern represents a new attempt at elucidating the mechanisms of keratinization mechanisms which are still unclear. We therefore studied the cytokeratin expression of the following types of ichthyosis: autosomal dominant ichthyosis vulgaris (n = 4), X-linked recessive ichthyosis vulgaris (n = 4), recessive non-bullous congenital ichthyosiform erythroderma (n = 1), recessive classical lamellar ichthyosis (n = 2), autosomal dominant lamellar ichthyosis (n = 1), and Netherton syndrome (n = 1). After dissection of frozen sections of the interfollicular epidermis, two-dimensional gel electrophoresis was performed. For immunofluorescence microscopy a panel of monoclonal cytokeratin antibodies (KG8.13, KK8.60, KA5 and AE1) was used. Cytokeratin polypeptide expression was basically unchanged compared with normal epidermis. In contrast, however, the antibody AE1 did not stain the basal cell layer in most types of ichthyosis, regardless of their genetic type. The cytokeratin polypeptides nos. 6 and 16, which are generally considered markers of hyperproliferation, were not expressed in either type of ichthyosis vulgaris (XRI or ADI), but were detected in trace amounts in various types of congenital ichthyosis.

Topics: Antibodies, Monoclonal; Biopsy; Chromosome Aberrations; Chromosome Disorders; Cytoskeletal Proteins; Cytoskeleton; Fluorescent Antibody Technique; Genes, Dominant; Genes, Recessive; Humans; Ichthyosis; Keratins; Peptides; Skin

Lectin application is used to study 12 cases of ichthyosis, 8 cases of Darier's disease and two of acrokeratosis verruciformis, establishing comparative patterns with normal skin.

Topics: Darier Disease; Humans; Ichthyosis; Keratins; Keratosis; Lectins; Skin; Staining and Labeling

A case of 'peeling skin syndrome' is reported. We have demonstrated a hitherto unreported keratohyalin abnormality and a four-fold increase of cellular retinoic acid binding protein, in one of two biopsies from an erythematous, scaling lesion.

Topics: Adult; Female; Humans; Ichthyosis; Keratins; Microscopy, Electron; Skin; Syndrome; Vitamin A

Ichthyosis vulgaris (IV) is an autosomal dominant, scaling disorder in which keratohyaline granules and filaggrin are reduced in or absent from the epidermis of affected individuals. Morphologic and biochemical markers of epidermal differentiation were studied in keratinocytes cultured from clinically unaffected skin of patients with IV, from clinically unaffected skin of an obligate gene carrier, and from normal skin of unaffected family members and an adult volunteer. Cultured keratinocytes from affected subjects formed thickened layers of scaly cells that failed to react with monoclonal antibody to filaggrin. In contrast, normal cells contained many large, immunoreactive granules. Electron microscopy confirmed the absence of keratohyaline granules in affected cells and the presence of large keratohyaline granules in normal cells. Immunoblot analysis of keratinocyte extracts from subjects with ichthyosis showed that profilaggrin was absent, but no differences in keratins were detected between affected and control cells. For all parameters, findings in cells of the clinically unaffected obligate gene carrier were intermediate between those from affected patients and controls. We conclude that keratinocytes cultured from patients with IV maintain structural and biochemical phenotypic characteristics of the disease in vitro.

Topics: Biopsy; Cells, Cultured; Epidermis; Filaggrin Proteins; Histocytochemistry; Humans; Ichthyosis; Immunochemistry; Immunologic Techniques; Keratins; Pedigree; Phenotype; Skin

Topics: Adolescent; Adult; Dermatitis, Atopic; Diagnosis, Differential; Epidermis; Genes, Dominant; Humans; Ichthyosis; Keratins

Ichthyosis vulgaris is an autosomal dominant disorder of keratinization characterized histologically by absent or reduced keratohyaline granules in the epidermis and mild hyperkeratosis. The basic defect in ichthyosis vulgaris is unknown. We have tested for the presence of filaggrin and its precursor, profilaggrin, in the epidermis of affected and unaffected individuals from 2 families with ichthyosis vulgaris and correlated its presence and relative quantity with ultrastructure findings in the same individuals. Filaggrin was present on stained sodium dodecyl sulfate gels and immunoblots of epidermal proteins from controls and unaffected family members. It was absent from the more severely affected individuals in each family and reduced in intensity in the less severely affected family members. Immunohistology in controls showed localization of filaggrin-related protein in the stratum corneum and within the granular layer. In contrast, tissue from affected individuals showed little or no reaction. Electron microscopic studies showed that keratohyaline granules were absent in 3 severely affected individuals, and reduced in number in the others. The relative amount of keratohyalin by electron microscopy correlated with the amount of filaggrin detectable on immunoblots. The stratum corneum was thicker than in normals but showed the typical "keratin pattern" staining suggesting that filaggrin is not essential for keratin filament aggregation and may have another function in vivo. We have demonstrated that the structural proteins, profilaggrin and filaggrin, are reduced or absent in 5 patients from 2 pedigrees with ichthyosis vulgaris. This biochemical abnormality correlates with the morphologic reduction in the amount of keratohyalin, and with the clinical severity of the disorder.

Topics: Adult; Electrophoresis, Polyacrylamide Gel; Epidermis; Female; Filaggrin Proteins; Histocytochemistry; Humans; Ichthyosis; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Male; Protein Precursors

Topics: Humans; Ichthyosis; Keratins; Research Support as Topic

Extensive morphological and biochemical studies were carried out on two sibling cases of ichthyosis linearis circumflexa. The condition was found to be similar to psoriasis in the following ways: effectiveness of PUVA therapy, psoriatic changes on light and electron microscopy, high urinary polyamine levels, elevation of several enzyme activities in the scales, and a remarkable change in keratin molecules. These results may reflect an increased epidermal proliferation with a reduced epidermal transit time, as occurs in psoriasis.

Topics: Adolescent; Adult; Amino Acids; Electrophoresis, Polyacrylamide Gel; Female; Humans; Ichthyosis; Keratins; Male; Microscopy, Electron; Polyamines; Psoriasis; Skin

Clinical and light and electron microscopic observations of a 16-year-old male patient suffering from ichthyosis hystrix (Curth-Macklin) are presented. The patient had no family history for this disease. The diagnosis was based on the distinct electron microscopic finding of continuous perinuclear tonofibril shells in the keratinocytes. About 10% of the keratinocytes were binucleate and one third contained conspicuous vacuoles. The steroid sulphatase activity in a skin biopsy was normal. Etretinate treatment proved beneficial during the first year of therapy. Later the treatment was less effective. The basic genetic defect persisted in the phenotype of the keratinocytes during etretinate therapy, but the exceedingly thick horny layer was considerably thinned.

Topics: Adolescent; Biopsy; Epidermolysis Bullosa; Etretinate; Humans; Ichthyosis; Keratins; Male; Microscopy, Electron; Skin

The ichthyotic skin in X-linked dominant chondrodysplasia punctata was investigated in a four-week-old baby and a fourteen-year-old girl. Histologically, the ichthyosiform erythroderma of the newborn and the ichthyosis of the older child presented as a retention hyperkeratosis with several distinctive features such as calcification of the keratotic follicular plugs, atrophy of the hair follicles and focal hyperpigmentation of the basal keratinocytes. On ultrastructural examination, small to medium sized vacuoles were regularly seen in the thinned granular layer. Some of these vacuoles contained needle-like calcium inclusions. The histologic and ultrastructural findings are therefore characteristic for this rare type of ichthyosis.

Topics: Adolescent; Chondrodysplasia Punctata; Female; Hair; Humans; Ichthyosis; Infant, Newborn; Keratins; Scalp Dermatoses; Skin; Vacuoles; X Chromosome

Topics: Electrophoresis, Polyacrylamide Gel; Gestational Age; Humans; Ichthyosis; Infant, Newborn; Keratins; Microscopy, Electron; Molecular Weight; Peptides; Skin; X-Ray Diffraction

The Sjögren-Larsson syndrome (SLS) is characterized by congenital ichthyosis, spastic dior tetraplegia and mental retardation. The inheritance is autosomal recessive. All 36 patients with SLS alive in Sweden in 1980 were studied with regard to ichthyosis. A slight or moderate generalized hyperkeratosis, less pronounced in the face, was already present at birth. Collodion-like membranes were never seen. The ichthyosis developed to its full extent during infancy. It was sometimes slight but most often moderate. Three types occurred in various combinations. The skin changes were concentrated in the neck, flexures and lower abdomen, in which regions the scales were often dark. The non-scaly hyperkeratosis produced characteristic and easily visible skin markings. Generalized erythema was rare, especially in adults. The DNA synthesis of the epidermis and the production of a horny layer were increased. Hair and nails were normal, as also was the ability to sweat.

Topics: Adolescent; Adult; Biopsy; Child; Child, Preschool; DNA; Female; Genes, Recessive; Humans; Ichthyosis; Infant, Newborn; Intellectual Disability; Keratins; Male; Middle Aged; Muscle Spasticity; Paralysis; Skin; Syndrome

A method to decrease subjectivity in assessing hyperkeratosis by application of quantitative measurements is proposed. The proportion of the depth of the stratum corneum to that of the total epidermis was measured on stained sections of tissue and termed the keratinization index (K.I.). Determinations showed that the K.I. varied with anatomical regions and was greater in different types of ichthyosis than in normal samples. Two indices were assessed, namely, K.I. which describes the ratio of cornified layer to total epidermis measured to the tips of the dermal papillae, and K.I. measured to the bases of the rete ridges. These two indices reflect the contour of the dermo-epidermal junction.

Topics: Ankle; Biopsy; Forearm; Hand; Histocytochemistry; Humans; Ichthyosis; Keratins; Skin

Topics: History, 20th Century; Humans; Ichthyosis; Keratins; Skin; Vitamin A Deficiency

An infant with phenotypic harlequin ichthyosis survived for nine months, then died a crib death. At autopsy, an enlarged, but structurally normal, thymus was found. Light microscopically, the epidermis showed massive hyperkeratosis and variable parakeratosis, and a stain for neutral fat was positive in the upper epidermis and stratum corneum. Electron microscopic study disclosed crystals resembling cholesterol and masses of autophagic vacuoles, many of them glutted with lipid, deposited within cells of the stratum corneum. Biochemically, cholesterol and triglyceride levels in the stratum corneum were sharply elevated (19.8 and 32.0 mg/g of dry weight, respectively). A defect in epidermal lipid metabolism is postulated.

Topics: Autopsy; Female; Histocytochemistry; Humans; Ichthyosis; Infant; Infant, Newborn; Keratins; Lipid Metabolism; Skin

Electron microscopy is shown to represent an effective tool in the early diagnosis of genetic disorders. On the basis of ultrastructural findings in various dominant and recessive types of ichthyoses and epidermolyses, defects of structural proteins of the skin proved to form the main intrinsic pathogenetic feature of some dominantly inherited types whereas quantitative impairments characterize their closely resembling recessive counterparts. Most of the diseases concerned severely disable the involved patients. Early diagnosis is therefore of high importance. In those cases where an exact diagnosis in newborn children is difficult or impossible with respect to their clinical features, electron microscopy provides the clinician with reliable and significant criteria to differentiate between closely resembling entities.

Topics: Epidermolysis Bullosa; Humans; Hyalin; Ichthyosis; Infant, Newborn; Keratins; Microscopy, Electron; Skin

Topics: Adolescent; Cell Transformation, Neoplastic; Humans; Ichthyosis; Infant, Newborn; Keratins; Melanoma; Nevus; Nevus, Pigmented; Skin Neoplasms; Warts

Interfollicular epidermis from back and tail of the recessive mutant mouse ichthyosis (ic/ic) was studied by histologic, histochemical, ultrastructural, and autoradiographic techniques and compared to heterozygous and Swiss S mouse epidermis. In the ic/ic mouse the stratum corneum was thickened, the granular layer prominent, and the stratum spinosum hyperplastic. Staining reactions for certain respiratory and lysosomal enzymes were more pronounced in epidermis of both back and tail. Ultrastructural studies of ic/ic epidermis demonstrated excessively clumped tonofilaments and increased numbers of mitochondria, ribonuclear protein particles, and membrane-coating granules in the stratum spinosum cells. Dilated intercellular junctions between the stratum spinosum and stratum granulosum cells were packed with membrane-coating and amorphous material. Profuse keratin-forming structures, abnormally large keratohyaline granules, and persistent mitochondria were seen in the stratum granulosum cells. In the stratum corneum, inclusions were prominent and persisted into the upper layers of cells, which were irregular in outline and greatly thickened. No differences in epidermal cell transit time or labeling index were demonstrated among the three types of mice.

Topics: Animals; Autoradiography; Disease Models, Animal; Histocytochemistry; Ichthyosis; Keratins; Mice; Microscopy, Electron; Skin

Topics: Genes, Dominant; Genes, Recessive; Humans; Hyalin; Ichthyosis; Keratins; Male; Sex Chromosomes; Skin

Topics: Adolescent; Adult; Child; Cytoplasmic Granules; Female; Histidine; Histocytochemistry; Humans; Ichthyosis; Keratins; Male; Middle Aged; Pedigree; Sex Chromosomes; Staining and Labeling; Tritium

Topics: Administration, Topical; Adolescent; Adult; Arm; Back; Biopsy; Child; Child, Preschool; Citrates; Female; Glucuronates; Glycolates; Humans; Hydroxy Acids; Hydroxybutyrates; Ichthyosis; Infant; Keratins; Lactates; Leg; Malates; Male; Pyruvates; Skin; Tartrates

Topics: Autopsy; Humans; Ichthyosis; Infant, Newborn; Keratins; Male; Skin

Topics: Cell Division; Desmosomes; Humans; Ichthyosis; Keratins; Microscopy, Electron; Mitosis; Skin; Skin Diseases, Vesiculobullous

Topics: Animals; Dogs; Histological Techniques; Hyalin; Ichthyosis; Keratins; Mice; Microscopy, Electron; Skin; Skin Diseases

Topics: Adult; Chromosome Aberrations; Chromosome Disorders; Darier Disease; Desmosomes; Hand; Humans; Hyalin; Ichthyosis; Keratins; Male; Nails, Malformed; Scleredema Adultorum; Skin; Sweating; Syndrome

Topics: Adolescent; Adult; Biopsy; Child; Chromosome Aberrations; Chromosome Disorders; Female; Humans; Ichthyosis; Keratins; Male; Microscopy, Electron; Middle Aged; Skin

Topics: Cell Nucleus; Chromosomes; Cytoplasmic Granules; Desmosomes; Diagnosis, Differential; Genes, Dominant; Genes, Recessive; Humans; Hyalin; Ichthyosis; Keratins; Microscopy, Electron; Ribosomes; Sex Chromosome Aberrations

Topics: Animals; Antibody Formation; Cattle; Electrophoresis, Polyacrylamide Gel; Humans; Hydrogen-Ion Concentration; Ichthyosis; Immunodiffusion; Immunoelectrophoresis; Keratins; Mammals; Psoriasis; Rabbits; Rats; Skin

Topics: Child; Female; Humans; Ichthyosis; Infant, Newborn; Keratins; Lipid Metabolism; Male

Topics: Animals; Cell Nucleus; Cytoplasmic Granules; Dogs; Golgi Apparatus; Humans; Ichthyosis; Keratins; Mice; Microscopy, Electron; Ribosomes; Skin

Topics: Cell Membrane; Child; Child, Preschool; Cytoplasmic Granules; Desmosomes; Ectodermal Dysplasia; Female; Hair; Humans; Ichthyosis; Keratins; Microscopy, Electron; Scalp Dermatoses; Skin; Syndrome

Topics: Animals; Cattle; Electrophoresis, Starch Gel; Humans; Ichthyosis; Keratins; Peptide Biosynthesis; Protein Biosynthesis; Proteins; Psoriasis; Skin; Species Specificity; Structure-Activity Relationship; X-Ray Diffraction

Topics: Amino Acids; Autoanalysis; Cadaver; Callosities; Chemical Precipitation; Chromatography, Gel; Dextrans; Electrophoresis, Polyacrylamide Gel; Humans; Hydrogen-Ion Concentration; Ichthyosis; Keratins; Protein Denaturation; Psoriasis; Skin; Tissue Extracts

Topics: Adolescent; Child; Child, Preschool; Ectodermal Dysplasia; Female; Hair; Humans; Ichthyosis; Infant; Keratins; Male; Microscopy, Electron; Scalp; Scalp Dermatoses

Topics: Alopecia; Biomechanical Phenomena; Elasticity; Female; Genetic Diseases, Inborn; Hair; Homocystinuria; Humans; Hyperthyroidism; Hypothyroidism; Ichthyosis; Keratins; Keratosis; Male; Oxidation-Reduction; Skin Diseases; Ultrasonography; X-Ray Diffraction

Topics: Blister; Dermatitis, Atopic; Dermatitis, Exfoliative; Extremities; Facial Dermatoses; Foot Dermatoses; Genes, Dominant; Genes, Recessive; Hand Dermatoses; Humans; Ichthyosis; Keratins; Keratosis; Microscopy, Electron; Ribosomes; Scalp Dermatoses; Sex Chromosomes; Skin; Thorax

Topics: Bone and Bones; Epithelium; Female; Fingers; Humans; Ichthyosis; Infant, Newborn; Infant, Newborn, Diseases; Keratins; Meconium; Muscles; Scalp; Skin; Thymus Gland; X-Ray Diffraction

Topics: Acids; Alcohols; Aldehydes; Capsules; Child; Erythema; Female; Humans; Ichthyosis; Keratins; Ointments; Vitamin A

Topics: Basement Membrane; Biopsy; Cytoplasm; Humans; Ichthyosis; Keratins; Microscopy, Electron; Mitochondria; Ribosomes; Skin

Topics: Carcinoma, Basal Cell; Humans; Ichthyosis; Keratins; Keratosis; Microscopy, Electron; Mitochondria; Psoriasis; Skin Neoplasms

Topics: Ectropion; Humans; Ichthyosis; Infant; Infant, Newborn; Infant, Newborn, Diseases; Keratins; Male

Topics: Hair; Humans; Hypersensitivity; Ichthyosis; Infant; Keratins; Male; Skin; Skin Diseases

Topics: Cell Membrane; Humans; Ichthyosis; Keratins; Microscopy, Electron; Mitochondria; Skin

Topics: DNA; Humans; Ichthyosis; In Vitro Techniques; Keratins; Psoriasis; Ribosomes; RNA; Skin

Topics: Adolescent; Biopsy; Female; Humans; Ichthyosis; Keratins; Keratosis; Male; Microscopy, Electron

Topics: Eczema; Electrophoresis; Esterases; Humans; Ichthyosis; Isoenzymes; Keratins; Psoriasis; Skin

Topics: Female; Humans; Ichthyosis; Infant, Newborn; Keratins

Topics: Humans; Ichthyosis; Ichthyosis, Lamellar; Keratins

Topics: Epidermis; Humans; Ichthyosis; Keratins; Psoriasis; Skin; X-Ray Diffraction