A new mutation in the type II hair cortex keratin hHb1 involved in the inherited hair disorder monilethrix

• Published in: Human genetics 1997-12, Vol.101 (2), p.165-169
• Main Authors: WINTER, H, ROGERS, M. A, GEBHARDT, M, WOLLINA, U, BOXALL, L, CHITAYAT, D, BABUL-HIRJI, R, STEVENS, H. P, ZLOTOGORSKI, A, SCHWEIZER, J
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; chromosome 12; Dermatology; Female; Germany; Hair - chemistry; Hair and nails disorders; Hair Diseases - genetics; Humans; Keratins - genetics; Male; Medical sciences; Molecular Sequence Data; Monilethrix; Mutation; Pedigree; Polymerase Chain Reaction; Sequence Analysis, DNA
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s004390050607

Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of monilethrix have been linked to the type II keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved glutamic acid residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the type II hair keratin hHb6 have recently been identified in monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the type II hair keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related type II hair keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that monilethrix is a disease of the hair cortex.