Atrichia with papular lesions resulting from a novel insertion mutation in the human hairless gene.
BACKGROUND: Congenital atrichia with papular lesions is a rare, recessively inherited condition of total alopecia, characterized clinically by complete and irreversible hair loss, which begins shortly after birth with the development of the papular lesions of keratin-filled cysts over an extensive area of the body. Mutations in the human hairless (HR) gene have been implicated in the pathogenesis of this disorder. OBJECTIVE: To search for a mutation in human HR in a family with congenital atrichia. METHODS: Linkage analysis was carried out using genotyping markers closely linked to congenital atrichia locus on chromosome 8p12. Subsequently, human HR was sequenced to identify a disease-causing mutation. RESULTS: A novel 11 bp insertion mutation, G202 (InsCTTCCCCCAGG), in exon 2 of the hairless gene was identified in a Pakistani consanguineous family affected by congenital atrichia. The insertion results in the expansion of 11 bp tandem repeat, which introduces a translational frameshift leading to downstream premature termination codon. CONCLUSIONS: This mutation is the first insertion mutation identified in the coding sequence of human HR. This extends our knowledge of mutations in HR that define the pathogenic basis of this disease.