title: Keratin 9 gene mutations in five Korean families with epidermolytic palmoplantar keratoderma.
abstract: Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant disease characterized clinically by localized palmoplantar thickening and histopathologically by granular degeneration of the epidermis. Recent molecular biological studies have revealed that EPPK is caused by mutations of the keratin 9 gene in sequences mainly encoding the highly conserved 1 A rod domain. Here we demonstrate a novel mutation of N160H (position 8 of the 1 A domain) and two other previously reported mutations, R162W and N160S, in five unrelated Korean families with EPPK. The three-dimensional structure of the 1 A domain of the related vimentin intermediate filament protein chain is now known. Based on its likely similarity to the keratin 9 chain, we predict that inappropriate amino acid substitutions in position 10 of 1 A will likely interfere with coiled-coil dimer stability, and those in position 8 will interfere with tetramer stability. Accordingly, these mutations compromise the structural integrity of the keratin intermediate filaments leading to the pathology of EPPK.
authors.affiliation: Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
authors.forename: Joo-Heung
authors.initials: JH
authors.lastname: Lee
authors.forename: Kwang-Sung
authors.initials: KS
authors.lastname: Ahn
authors.forename: Cha-Hui
authors.initials: CH
authors.lastname: Lee
authors.forename: Seong-Jae
authors.initials: SJ
authors.lastname: Youn
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Dong-Youn
authors.initials: DY
authors.lastname: Lee
authors.forename: Eil-Soo
authors.initials: ES
authors.lastname: Lee
authors.forename: Peter M
authors.initials: PM
authors.lastname: Steinert
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004247:DNA / Q000737:chemistry; D019281:Dimerization; D005192:Family Health; D005260:Female; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000235:genetics*; D007633:Keratins / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D007723:Korea; D008297:Male; D009154:Mutation; D010375:Pedigree; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary
chemical_list: D010455:Peptides; D007633:Keratins; D004247:DNA