Monilethrix: Mutational hotspot in the helix termination motif of the human hair basic keratin 6

Monilethrix is a rare autosomal dominant disease characterized by hair frag ility and follicular hyperkeratosis. Mutations in the human basic hair kera tins hHb1 and hHb6 have recently been reported in this disease. Twelve fami lies and sporadic cases were clinically diagnosed with monilethrix and were available for the study. The gene segment encoding the helix termination m otif region of keratin hHb6 was PCR amplified and sequenced. Mutations were recognized in 6 families. Four families had the previously described mutat ions, Glu413Lys and Glu413Asp, In 2 unrelated families, a novel mutation, G lu402Lys, was identified. No clear association was found between the severi ty of the phenotype and the mutation carried. Furthermore, heterozygous mem bers of the same family had variable degrees of hair and skin involvement. Homozygous patients identified in one large consanguineous family were more severely affected. Other genetic or environmental factors may also play a role in monilethrix. Copyright (C) 2000 S. Karger AG, Basel.