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A mutation in the V1 end domain of keratin 1 in non-epidermolytic palmar-plantar keratoderma.

Authors
  • Kimonis, V
  • DiGiovanna, J J
  • Yang, J M
  • Doyle, S Z
  • Bale, S J
  • Compton, J G
Type
Published Article
Journal
The Journal of investigative dermatology
Publication Date
Dec 01, 1994
Volume
103
Issue
6
Pages
764–769
Identifiers
PMID: 7528239
Source
Medline
License
Unknown

Abstract

Mutations in keratin 9 have been found in families with an epidermolytic form of palmar-plantar keratoderma (PPK). In another form of PPK (Unna-Thost type), epidermolysis is not observed histologically. We studied a pedigree with this non-epidermolytic form of PPK. By gene linkage analysis, the type I keratin locus could be excluded but complete linkage with the type II keratin region was found. Sequence analysis identified a single base change in the amino-terminal V1 variable subdomain of keratin 1, which caused a lysine to isoleucine substitution. This non-conservative mutation completely cosegregated with the disease and was not observed in 50 unrelated unaffected individuals. An examination of keratin amino-terminal sequences revealed a previously unreported 22-residue window in the V1 subdomain that is conserved among most type II keratins. The altered lysine is an invariant residue in this conserved sequence. Previously described keratin mutations affect the central regions important for filament assembly and stability, and cause diseases characterized by cellular degeneration or disruption. This is the first disease mutation in a keratin chain variable end region. The observation that it is not associated with epidermolysis supports the concept that the amino-terminal domain of keratins may be involved in supramolecular interactions of keratin filaments rather than stability. Therefore, hyperkeratosis associated with this mutation may be due to perturbations in the interactions of the keratin end domain with other cellular components.

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