bromochloroacetic-acid and Diseases-in-Twins

To assess the genetic effect on the occurrence of rheumatoid arthritis (RA) associated autoantibodies.. A co-twin control study of 27 monozygotic (MZ) and 51 dizygotic same sexed (DZss) RA discordant twins.. The probandwise concordance rate of anti-keratin antibodies (AKA), anti-cyclic citrullinated peptide antibodies (ACPA), IgA- and IgM rheumatoid factor (IgA-RF and IgM-RF). The odds ratio for these autoantibodies based on both conditional and unconditional logistic regression adjusting for the two major genetic risk factors as well as smoking.. The probandwise concordance rates (95% CI) of ACPA, AKA, IgM-RF and IgA-RF were 78.6 (55.4-92.4), 16.7 (0.6-58.4), 30.0 (7.3-60.6), 42.1 (14.5-71.1) in MZ twins and 25.0 (10.3-44.4), 0.0 (0.0-27.7), 10.5 (1.4-31.5) and 22.2 (6.8-45.0) in DZss twins. In twin pairs discordant for both RA and autoantibodies the OR of ACPA, AKA, IgM-RF and IgA-RF was 5 (0.5-236.5) 9 (1.3-394.5) 272 (3.5-593.2) and 10 (1.4-434.0) in MZ twin pairs and 17 (4.4-146.1) 20 (3.2-828.0) 33 (5.5-1342.4) and 577 (7.4-1149.2) in DZss twin pairs. In multiple logistic regression analysis on ACPA, the MZ/DZ OR was 21.1 (3.3-213.5) when adjusting for age, sex, ever smoking, PTPN22 1858 T-allele, Shared Epitope (SE) and SE-smoking interaction.. There is a genetic contribution to ACPA generation independent of both SE and PTPN22 1858 T-allele. Environmental factors may trigger the expression of IgA-RF, ACPA and AKA in healthy persons who are predisposed to RA.

Topics: Aged; Alleles; Arthritis, Rheumatoid; Autoantibodies; Diseases in Twins; Female; Genetic Predisposition to Disease; Genotype; HLA-DRB1 Chains; Humans; Keratins; Logistic Models; Male; Middle Aged; Multivariate Analysis; Peptides, Cyclic; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Rheumatoid Factor; Smoking; Twins, Dizygotic; Twins, Monozygotic

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

Extensive epidermal necrosis in newborn infants is an unusual event of heterogeneous cause.. The objective of this article is to describe what seems to be a previously unrecognized lethal disease.. The clinical and histopathologic features of three premature infants, two of them nonidentical twins, and the autopsy findings of one of them were analyzed.. Intrauterine lethal epidermal necrosis with hair follicle calcification, except for the face, hands, feet, elbows, and knees, was present in all three patients. Some histopathologic features were suggestive of epidermal apoptosis.. We propose that the clinicopathologic alterations in our patients represent a new condition that may be caused by massive epidermal apoptosis.

Topics: Apoptosis; Calcinosis; Collagen; Diseases in Twins; Elbow; Epidermis; Face; Fatal Outcome; Female; Fetal Diseases; Foot; Hair Diseases; Hair Follicle; Hand; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Keratinocytes; Keratins; Knee; Necrosis; Skin; Skin Abnormalities; Twins, Dizygotic

Epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma) is an autosomal dominant skin disorder caused by defects in the suprabasal keratins. Recently, mutations in the keratins 1 and 10 have been identified in patients with this disease. In this study, direct gene sequencing was used to establish the prenatal diagnosis in 15-week gestation twins at risk for epidermolytic hyperkeratosis. Direct sequence analysis of genomic DNA from the affected father and from both chorionic villus samples revealed a tyrosine to asparagine mutation at position 14 within the highly conserved 1A alpha-helical segment of keratin 10. None of the unaffected family members that were analyzed exhibit this mutation nor have polymorphic variations been observed in the normal population at this position. This residue is invariant in all type I keratins sequenced to date and is also conserved in related intermediate filament proteins such as vimentin and lamin. Given this high degree of conservation it is probable that any mutation at this position is deleterious and will result in disease.

Topics: Adult; Base Sequence; Chorionic Villi; Diseases in Twins; DNA; Female; Fetal Diseases; Genes, Dominant; Humans; Hyperkeratosis, Epidermolytic; Keratins; Laminin; Male; Molecular Sequence Data; Mutation; Pedigree; Prenatal Diagnosis; Risk Factors; Sequence Analysis, DNA; Vimentin