163 Mutation in the type II hair keratin in the patients with inherited hair disorder monilethrix

Woo-Young Sim, Dong-Ju Ha, Sung-Soo Kim* Department of Dermatology, *Department of Molecular Biology, College of Medicine, Kyung Hee University, Seoul, Korea

Monilethrix is an rare autosomal dominant hair disorder characterized by increased hair fragility, keratosis pilaris, and unique beaded morphology. Recently pathogenic mutations in the helix termination and helix initiation motif of two type II human hair cortex keratin (hHb1, hHb6) genes have been identified in monilethrix patients. A 24-year-old Korean woman presented with progressive hair loss and emergence of short brittle hair which started at low occipital area from the age of 4 months. Physical examination revealed keratosis pilaris on both thighs. Family history showed 12 clinically affected individuals in three generation, which exhibited inheritance pattern of autosomal dominant. On light microscopy, the regular, dark beads were seen alternating with the pale constriction of the internodes. We have studied hair keratin genes with DNA extracted from the peripheral blood lymphocytes of clinically affected individuals (the patient and her mother) and clinically non-affected individuals (two sisters of the patient). PCR was used to amplifying genomic DNA fragments containing the coding sequences for á-helical 1A, 1B, 2A, and 2B subdomains of the type II hair cortex keratins hHb1 and hHb6. The PCR products were subcloned into pGEM T vector by standard subcloning technique. The subcloned DNA was purified from each E. coli colonies and used for DNA sequencing. DNA sequence was determined by the dideoxy-chain termination method using a T7 sequenase version 2.0 kit (USB, Cleveland, OH). By examining the rod domains of hHb1 and hHb6, we have identified novel point mutation in exon 4 of hHb6 in the patient and her mother. The mutation affected the second base of codon 220 (G to A transition), leading to histidine substitution of arginine residue. The sequence of the 1A and 2B helical regions of hHb1 and hHb6 were normal. We report a novel mutation of hHb6 R220H in a family with monilethrix