Keratin 9 gene mutations in five Korean families with epidermolytic palmoplantar keratoderma.
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.
Lee
Joo-Heung
JH
Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
Ahn
Kwang-Sung
KS
Lee
Cha-Hui
CH
Youn
Seong-Jae
SJ
Kim
Jong-Wook
JW
Lee
Dong-Youn
DY
Lee
Eil-Soo
ES
Steinert
Peter M
PM
Yang
Jun-Mo
JM
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
D010455:Peptides; D007633:Keratins; D004247:DNA