Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

The Genetic Basis of Weber-Cockayne Epidermolysis Bullosa Simplex

Yiu-Mo Chan, Qian-Chun Yu, Jo-David Fine and Elaine Fuchs
Proceedings of the National Academy of Sciences of the United States of America
Vol. 90, No. 15 (Aug. 1, 1993), pp. 7414-7418
Stable URL: http://www.jstor.org/stable/2362724
Page Count: 5
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
The Genetic Basis of Weber-Cockayne Epidermolysis Bullosa Simplex
Preview not available

Abstract

Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant skin diseases characterized by blistering, due to mechanical-stress-induced degeneration of basal epidermal cells. Recently, it was discovered that the more severe types, Dowling-Meara and Koebner, are genetic disorders of the basal epidermal keratins, keratin 5 (K5) and keratin 14 (K14). Here, we show that the mildest type of EBS, Weber-Cockayne, is also a disorder of these keratins. Affected members of two unrelated families with Weber-Cockayne EBS had a T → G point mutation in the second base position of codon 161 of one of two K5 alleles, leading to an Ile → Ser mutation. This mutation was not present in unaffected members or in 156 alleles from normal individuals. Linkage analyses mapped the defect to the type II keratin gene cluster on chromosome 12q11-q13 (peak logarithm of odds score at θ = 0 of 3.0), providing strong additional evidence that this mutation is responsible for the Weber-Cockayne EBS phenotype. Conserved among type II keratins, Ile-161 is in the nonhelical head domain of K5, a region previously shown to be important for 10-nm filament assembly. The mutation generates a potential substrate site for protein kinase C, which could influence intermediate filament architecture, perhaps leading to the intrafilament association seen ultrastructurally in patients with the mutation.

Page Thumbnails

  • Thumbnail: Page 
7414
    7414
  • Thumbnail: Page 
7415
    7415
  • Thumbnail: Page 
7416
    7416
  • Thumbnail: Page 
7417
    7417
  • Thumbnail: Page 
7418
    7418