Linkage of epidermolytic hyperkeratosis to the type II keratin gene cluster on chromosome 12q

• Published in: Nature genetics Vol. 1; no. 4; pp. 301 - 305
• Main Authors: Compton, John G, DiGiovanna, John J, Santucci, Sandra K, Kearns, Kathleen S, Amos, Christopher I, Abangan, Donita L, Korge, Bernhard P, McBride, O. Wesley, Steinert, Peter M, Bale, Sherri J
• Format: Journal Article
• Language: English
• Published: United States 01.07.1992
• Subjects: Base Sequence; Chromosome Mapping; Chromosomes, Human, Pair 12; DNA - genetics; DNA - isolation & purification; DNA, Satellite - genetics; Female; Genetic Linkage; Genetic Markers; Genotype; Humans; Hyperkeratosis, Epidermolytic - genetics; Hyperkeratosis, Epidermolytic - pathology; Keratins - genetics; Lod Score; Male; Molecular Sequence Data; Multigene Family; Oligodeoxyribonucleotides; Polymerase Chain Reaction - methods; Polymorphism, Restriction Fragment Length; Skin - pathology
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0792-301

We investigated the molecular genetics of epidermolytic hyperkeratosis (EHK), a dominant disorder characterized by epidermal blistering, hyperkeratosis, vacuolar degeneration and clumping of keratin filaments. Based on this pathology, we have excluded by linkage analysis several candidate genes for the disease; in contrast, complete linkage was obtained with the type II keratin, K1, on 12q11-q13. Linkage in this region of chromosome 12 was confirmed using several other markers, and multi-locus linkage analyses further supported this location. Keratins are excellent EHK gene candidates since their expression is specific to the suprabasal epidermal layers. In the pedigree studied here, a type II keratin gene, very probably K1, is implicated as the site of the molecular defect causing EHK.