title: A homozygous nonsense mutation in the human desmocollin-3 (DSC3) gene underlies hereditary hypotrichosis and recurrent skin vesicles.
abstract: Desmosomes are the major players in epidermis and cardiac muscles and contribute to intercellular binding and maintenance of tissue integrity. Two important constituents of desmosomes are transmembrane cadherins named desmogleins and desmocollins. The critical role of these desmosomal proteins in epithelial integrity has been illustrated by their disruption in mouse models and human diseases. In the present study, we have investigated a large family from Afghanistan in which four individuals are affected with hereditary hypotrichosis and the appearance of recurrent skin vesicle formation. All four affected individuals showed sparse and fragile hair on scalp, as well as absent eyebrows and eyelashes. Vesicles filled with thin, watery fluid were observed on the affected individuals' scalps and on most of the skin covering their bodies. A scalp-skin biopsy of an affected individual showed mild hair-follicle plugging. Candidate-gene-based homozygosity linkage mapping assigned the disease locus to 8.30 cM (8.51 Mbp) on chromosome 18q12.1. A maximum multipoint LOD score of 3.30 (theta = 0.00) was obtained at marker D18S877. Sequence analysis of four desmoglein and three desmocollin genes, contained within the linkage interval, revealed a homozygous nonsense mutation (c.2129T>G [p.Leu710X]) in exon-14 of the desmocollin-3 (DSC3) gene.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayub
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.forename: Musharraf
authors.initials: M
authors.lastname: Jelani
authors.forename: Fazal
authors.initials: F
authors.lastname: Ur Rehman
authors.forename: Muhammad
authors.initials: M
authors.lastname: Iqbal
authors.forename: Masoom
authors.initials: M
authors.lastname: Yasinzai
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000293:Adolescent; D000818:Animals; D001706:Biopsy; D002648:Child; D002874:Chromosome Mapping; D018389:Codon, Nonsense; D051187:Desmocollins / Q000235:genetics* / Q000378:metabolism; D051182:Desmogleins / Q000235:genetics; D003896:Desmosomes / Q000473:pathology; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D051379:Mice; D012867:Skin / Q000473:pathology*; D012871:Skin Diseases / Q000235:genetics / Q000473:pathology*
chemical_list: D018389:Codon, Nonsense; C490356:DSC3 protein, human; D051187:Desmocollins; D051182:Desmogleins