title: Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly hair/hypotrichosis in Pakistani families.
abstract: Autosomal dominant woolly hair (ADWH) is an inherited condition of tightly curled and twisted scalp hair. Recently, a mutation in human keratin-74 (KRT74) gene has been shown to cause this form of hereditary hair disorder. In the present study, we have described two families (A and B) having multiple individuals affected with autosomal dominant form of hair loss disorders. In family A, 10 individuals showed ADWH phenotype while in the family B, 14 individuals showed hypotrichosis of the scalp. Genotyping using polymorphic microsatellite markers showed linkage of both the families to type II keratin gene cluster on the chromosome 12q12-14.1. Mutation analysis of the KRT74 gene identified two novel mutations in the affected individuals of the families. The sequence analysis revealed a splice acceptor site mutation (c.IVS8-1G>A) in family A and a missense variant (c.1444G>A, p.Asp482Asn) in family B. Mutations identified in the present study extend the body of evidence implicating the KRT74 gene in the pathogenesis of autosomal dominant hair loss disorders.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Naveed
authors.initials: N
authors.lastname: Wasif
authors.forename: Syed Kamran ul-Hassan
authors.initials: SK
authors.lastname: Naqvi
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.forename: Nadir
authors.initials: N
authors.lastname: Ali
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006201:Hair Diseases / Q000151:congenital / Q000235:genetics; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D053564:Keratins, Hair-Specific / Q000235:genetics*; D053531:Keratins, Type II / Q000235:genetics*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010154:Pakistan; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: C473406:KRT74 protein, human; D053564:Keratins, Hair-Specific; D053531:Keratins, Type II; D022821:RNA Splice Sites