MONILETHRIX - A KERATIN HHB6 MUTATION IS CODOMINANT WITH VARIABLE EXPRESSION

Monilethrix is a rare autosomal dominant disease characterized by hair fragility and hyperkeratotic papules. Mutations in type-II hair speci fic keratins hHb6 and hHb1 have recently been reported. We describe a large family with a E410D mutation in the evolutionary conserved helix termination motif of keratin hHb6 that was variably expressed among 1 2 heterozygous members, and severely expressed among 3 homozygous memb ers. These 3 patients had essentially complete lack of scalp hair sinc e the age of 2 months with no improvement over time as well as follicu lar keratotic involvement extensively expressed over the scalp and lar ge body areas. The variability seen in heterozygous patients, along wi th seasonal and pregnancy-related improvement suggest that other genet ic or environmental factors may modify keratin gene expression. This r epresents the first report of a co-dominant keratin hHb6 mutation resu lting in severe disease.