Ayub et al. (2009) studied a consanguineous Afghan family in which 3 sisters, 12 to 18 years of age, and their 5-year-old brother displayed features of hereditary hypotrichosis, associated with vesicles on the scalp and skin. At birth, ... Ayub et al. (2009) studied a consanguineous Afghan family in which 3 sisters, 12 to 18 years of age, and their 5-year-old brother displayed features of hereditary hypotrichosis, associated with vesicles on the scalp and skin. At birth, scalp hair was present, and after ritual shaving at 1 week of age, scalp hair grew back; however, the hair was fragile and began falling out at 2 to 3 months of age, eventually leaving only sparse hair on the scalp. Vesicles that were less than 1 cm in diameter were observed on the scalp and skin of most of the body, occasionally disappearing but then reappearing; intermittently, the vesicles would burst with a release of fluid, leaving scars on the site that took 3 to 4 months to heal. There were no mucosal vesicles. Upon examination, the affected individuals were nearly devoid of eyebrows, eyelashes, axillary hair, and body hair. Teeth, nails, palms, soles, sweating, and hearing were normal, as was electrocardiography. Serum IgA, IgE, and IgD were measured in 1 individual and showed no change compared to controls. The parents were clinically unaffected. A scalp biopsy of the 18-year-old sister showed slight follicular plugging, mild perivascular and periadnexal inflammatory cell presence, and normal hair follicles. The sebaceous glands appeared morphologically normal and connected to the hair follicles. Payne (2010) raised the question of whether clinical photographs in the article by Ayub et al. (2009) showed skin vesicles or keratosis pilaris (604093), noting that the scalp biopsy showed follicular plugging but no evidence of blistering. Payne (2010) suggested that because keratosis pilaris is a common disorder, affecting up to 40% of the adult population, further studies would be necessary to conclude that DSC3 gene mutations (see MOLECULAR GENETICS) cause an epidermal phenotype in affected patients. In response, Ahmad (2010) stated that 'we have absolutely no doubt that the features of the skin we have discussed in the article are correct' and noted that they had not seen similar lesions in any of more than 200 other Afghan individuals living in Pakistan nor in unaffected members of the family reported by Ayub et al. (2009).
In a consanguineous Afghan family with hypotrichosis and recurrent skin vesicles mapping to chromosome 18q12.1, Ayub et al. (2009) sequenced the DSG4 gene (607892), which had previously been associated with hypotrichosis (LAH1; 607903), but found no mutations. They ... In a consanguineous Afghan family with hypotrichosis and recurrent skin vesicles mapping to chromosome 18q12.1, Ayub et al. (2009) sequenced the DSG4 gene (607892), which had previously been associated with hypotrichosis (LAH1; 607903), but found no mutations. They then sequenced 3 additional desmoglein genes and 3 desmocollin genes located adjacent to DSG4 on chromosome 18q12.1, and identified homozygosity for a nonsense mutation in the DSC3 gene (600271.0001) in the 4 affected individuals. The unaffected parents and 3 healthy sibs were heterozygous for the mutation, which was not found in 100 unrelated ethnically matched controls.