LINKAGE OF MONILETHRIX TO THE TRICHOCYTE AND EPITHELIAL KERATIN GENE-CLUSTER ON 12Q11-Q13

Monilethrix is characterized by beaded or moniliform hair, which resul ts from the periodic thinning of the hair shaft. The beaded hair thus produced is subject to excess weathering and premature fracturing at t he internodes. Clinically, monilethrix presents with short, fragile, b roken hair. The follicular abnormalities range from subtle perifollicu lar erythema and hyperkeratosis to horny follicular papule formation. At the ultrastructural level, cytolysis and keratin tonofilament clump ing (epidermolysis) are seen in the cortical cells of the bulb of the hair follicle. Microsatellite markers flanking the keratin gene cluste rs at 17q12-q21 and 12q11-q13 were used to perform linkage analysis in a monilethrix pedigree. This study demonstrates linkage of monilethri x in a pedigree to microsatellite DNA loci mapping to the region on ch romosome 12 containing the type II keratin cluster. A major group of s tructural hair proteins, the basic type II trichocyte keratins, map wi thin this epithelial cytokeratin gene cluster. This study implicates a mutation in a trichocyte keratin gene in the pathogenesis of a struct ural hair disorder.