bromochloroacetic-acid and Hypotrichosis

The mammalian hair follicle (HF) is an active skin appendage which operates hair cycles throughout life. Recent advances in molecular genetics have led to the identification of many genes expressed in the HF. Furthermore, mutations in some of these genes have been shown to underlie congenital hair loss disorders in humans. Patients with congenital hair loss disorders can show various hair shaft anomalies, such as woolly hair and monilethrix. In the Japanese populations, most patients with congenital woolly hair/hypotrichosis possess common founder mutations in the lipase H (LIPH) gene. Identification of the causative genes for hair loss disorders directly demonstrates crucial roles of these genes in HF morphogenesis, development and/or hair growth in humans.

Topics: Cadherins; Desmosomes; Hair Diseases; Humans; Hypotrichosis; Keratins; Lipid Metabolism; Transcription Factors

The gene encoding human desmoglein 4 (DSG4) was recently cloned, and a mutation in this gene has been reported in several consanguineous Pakistani families affected with localized autosomal recessive hypotrichosis (LAH). In addition, various mutations in the Dsg4 gene have been identified in animal models of hypotrichosis that share a characteristic phenotype called "lanceolate hair". To date, the features of the hair-shaft anomaly in patients with LAH have not been well described. We report a Japanese patient affected with congenital hypotrichosis that was originally diagnosed as monilethrix because she had a hair-shaft abnormality that resembled moniliform hair. However, no mutations were found in the type II hair keratin genes, hHb1, hHb3, and hHb6, whose mutations cause monilethrix. Instead, we identified novel compound heterozygous mutations in the DSG4 gene of our patient. On the maternal allele is a novel S192P transition within the extracellular cadherin II domain of DSG4; on the paternal allele is a novel 2039insT mutation leading to the generation of unstable transcripts. Here we present the observation that mutations in the DSG4 gene can cause monilethrix-like congenital hypotrichosis. Based on our findings, we propose that LAH and monilethrix could overlap.

Topics: Alleles; Amino Acid Sequence; Child, Preschool; Desmogleins; DNA Mutational Analysis; Female; Hair; Hair Diseases; Heterozygote; Humans; Hypotrichosis; Keratins; Microscopy, Electron, Scanning; Molecular Sequence Data; Mutation; RNA Stability; Transcription, Genetic

Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair due to periodic thinning of the shaft. This disorder has been reported to be caused by mutations in the helix termination motif of two type II cortex keratins, hHb1 and hHb6. Here we describe a Japanese monilethrix family that has the most frequent mutation, the E413K mutation in hHb6, so far found in 26 families. Genotype/phenotype correlation was not obvious in our case or in the previously reported cases.

Topics: Child, Preschool; Codon; Female; Hair; Humans; Hypotrichosis; Japan; Keratins; Pedigree; Point Mutation; Polymerase Chain Reaction

The dermal histology of 9-week-old hairless rats derived from Wistar rats was investigated and compared with that of age-matched Wistar rats. Skin samples were taken from 4 portions: the head, dorsal and ventral skin, and foot pad. The epidermis of the 3 portions other than the foot pad was thicker in hairless rats than in Wistar rats. The hair canals of hairless rats contained lamellar cornified tissues instead of hair, and some of the hair follicles deep in the dermis exhibited cyst formation. S-100-immunoreactive cells were detected in the basal layer of epidermis and their number in hairless rats was greater than that in Wistar rats. Ultrastructurally, electron-lucent cells, i.e. Langerhans cells, which contained Birbeck granules and/or cored tubules, were observed more frequently in the epidermis of hairless rats than in that of Wistar rats. Some cells in one hairless rat, which had similar characteristics to Langerhans cells without Birbeck granules, contained confronting cisternae.

Topics: Animals; Cytoplasmic Granules; Epidermis; Hypotrichosis; Immunohistochemistry; Keratins; Langerhans Cells; Microscopy, Electron; Mutation; Rats; Rats, Mutant Strains; Rats, Wistar; Skin