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 fora 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 chromosome8p12.Subsequently,human HR was sequenced toidentify a disease-causing mutation.Results.A novel 11 bpinsertion mutation,G202(InsCTTCCCCCAGG),in exon 2 ofthe hairless gene was identified in a Pakistani consanguineous family affected by congenital atrichia.The insertion resultsin the expansion of 11 bp tandem repeat,which introducesa translational frame shift 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.
