Mutations in the hair cortex keratin hHb6 cause the inherited hair disease monilethrix

Nat Genet. 1997 Aug;16(4):372-4. doi: 10.1038/ng0897-372.


Pathogenic mutations in a large number of human epithelial keratins have been well characterized. However, analogous mutations in the hard alpha-keratins of hair and nail have not yet been described. Monilethrix is a rare autosomal dominant hair defect with variable expression. Hairs from affected individuals show a beaded structure of alternating elliptical nodes and constrictions (internodes). These internodes exhibit a high prospensity to weathering and fracture. Strong evidence that trichocyte keratin defects might underlie this hair disorder was provided by genetic linkage analyses that mapped this disease to the type-II keratin gene cluster on 12q13. All affected individuals from a four-generation British family with monilethrix, previously linked to the type-II keratin gene cluster, as well as three unrelated single monilethrix patients, exhibited a heterozygous point mutation in the gene for type-II hair cortex keratin hHb6, leading to lysine substitution of a highly conserved glutamic acid residue in the helix termination motif (Glu 410 Lys). In a three-generation French family with monilethrix of a milder and variable phenotype, we detected another heterozygous point mutation in the same glutamic acid codon of hHb6, which resulted in a conservative aspartic acid substitution (Glu 410 Asp). These mutations provide the first direct evidence for involvement of hair keratins in hair disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Female
  • Glutamic Acid
  • Hair Diseases / genetics*
  • Hair Diseases / pathology
  • Heterozygote
  • Humans
  • Keratins / genetics*
  • Lysine
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree


  • Glutamic Acid
  • Keratins
  • Lysine