A GENE FOR MONILETHRIX IS CLOSELY LINKED TO THE TYPE-II KERATIN GENE-CLUSTER AT 12Q13

Monilethrix is an uncommon hereditary disorder of hair and nail which produces hair fragility and a variable alopecia, Many of the dystrophi c hairs have a unique beaded morphology, Ultrastructural changes sugge st a defect in the microfilament structure of the cortex of the hair s haft, and hence the cysteine-rich trichocyte keratins are candidate ge nes, Here, in two families with autosomal dominant monilethrix, we hav e excluded linkage to the type I keratin gene cluster on chromosome 17 q, but show that the disorder is closely linked to the type II keratin cluster on 12q, where genes for basic trichocyte keratins are found. The combined maximum lod score for D12S96 was 12.27 at theta = 0.0, Th is is the first mapping of a primary human hair disorder and the first evidence implicating a defect of the 'hard' keratins of hair and nail in disease.