MAPPING OF MONILETHRIX TO THE TYPE-II KERATIN GENE-CLUSTER AT CHROMOSOME 12Q13 IN 3 NEW FAMILIES, INCLUDING ONE WITH VARIABLE EXPRESSIVITY

Monilethrix is an autosomal dominant disorder chiefly affecting hair, The degree of hair dystrophy is highly variable, as is the presence of additional features, such as follicular keratoses. In three British f amilies of monilethrix, linkage has recently been reported to the type II keratin gene cluster at chromosome 12q13, and it has been suggeste d that the disease is due to a defect in the hard keratins of hair and nail, If monilethrix is a keratin disorder, we would predict that som e pedigrees might map to the type I keratin gene cluster on 17q where hard keratin genes are also found, We have now studied clinically and by linkage analysis three new and unrelated pedigrees from England, Sc otland and Spain, the first of which showed a variant phenotype, In th is family the disease was expressed in four of 12 cases only as a foll icular keratosis of the neck, elbows and knees, and without clinical o r historical evidence of hair anomalies; non-penetrance :in an obligat e carrier was also observed, In all three families, we have establishe d linkage to a series of microsatellite markers at the type II locus a t 12q13 (Z(max) = 6.34 at theta = 0.00 for D12S368) and have excluded linkage from the type I keratin gene cluster on 17q. It remains probab le that monilethrix is a disorder of hard keratins, but at present the re is no evidence that it is due to defects in type I keratins.