A VARIABLE MONILETHRIX PHENOTYPE ASSOCIATED WITH A NOVEL MUTATION, GLU402LYS, IN THE HELIX TERMINATION MOTIF OF THE TYPE-II HAIR KERATIN HHB1

Monilethrix is a rare human hair disorder with autosomal dominant tran smission that can be caused by mutations in hair keratins, Up until no w, pathogenic mutations in the type II hair cortex keratins hHb6 and h Hb1 were restricted to a highly conserved glutamic acid residue Glu413 (Glu117 of the 2B subdomains) in the EIA-TYRRLLwEG (E) under bar E he lix termination motif of the two keratins. The critical glutamic acid residue was substituted either by a lysine or, less frequently, by an aspartic acid residue. Here we report a novel mutation in a French mon ilethrix family, which again consists of a lysine substitution of anot her highly conserved glutamic acid residue, Glu402 (Glu106 of the 2B s ubdomain), in the (E) under bar LATYRRLLEGEE motif of hHb1. Family mem bers bearing the hHb1 Glu402Lys mutation exhibit a particularly variab le disease phenotype, The pedigree comprises two infant members, one w ith pronounced dystrophic alopecia, follicular keratosis, and clear-cu t moniliform hair, and one with no hair loss at all and moniliform hai r detectable only by electron microscopy, as well as an adult individu al without any clinically or electron microscopically detectable sympt oms, but with clear historical proof of the disease.