A Mutation in the Hair Matrix and Cuticle Keratin KRTHB5 Gene Causes Ectodermal Dysplasia of Hair and Nail Type

The study investigated the genetic basis of a form of ectodermal dysplasia affecting hair and nails in a large Pakistani consanguineous family. Researchers mapped the disease locus to a 16.6 centimorgan region on chromosome 12q12–q14.1, which contains six type II hair keratin genes. A homozygous missense mutation in the KRTHB5 gene was identified, resulting in a histidine substitution for a conserved arginine residue (R78H) in the head domain. This finding provided the first direct evidence of the molecular pathogenesis of pure hair–nail ectodermal dysplasias.