Rapid Communication

Journal of Investigative Dermatology (1993) 101, 240–243; doi:10.1111/1523-1747.ep12365079

A Keratin 14 Mutational Hot Spot for Epidermolysis Bullosa Simplex, Dowling-Meara: Implications for Diagnosis

Karen Stephens1, Virginia P Syber2,3, Ellen M Wijsman1,4, Pamela Ehrlich1 and Anne Spencer2

  1. 1Division of Medical Genetics, Department of Medicine, University of Washington
  2. 2Divisions of Medical Genetics and Dermatology, Departments of Medicine and Pediatrics, University of Washington
  3. 3Children's Hospital and MedicalCenter University of Washington, Seattle, Washington, U.S.A.
  4. 4Department of Biostatistics, University of Washington, Seattle, Washington, U.S.A.

Received 5 February 1993; Accepted 12 April 1993.

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Abstract

Recently, two patients with the Dowling-Meara subtype of epidermolysis bullosa simplex (EBS-DM) were reported with different mutations in codon 125 of the keratin 14 gene. To determine whether these are common mutations, we screened ten EBS-DM patients and their families using single nucleotide primer extension. Four of ten unrelated EBS-DM patients had a Gright arrowA substitution at base pair 434 of codon 125, whereas one case out often had a Cright arrowT substitution at position 433 of the same codon. The G434A alteration cosegregated with the disorder in two multigenerational families; no recombination events were detected. In these two families, linkage analysis provided significant evidence in favor of linkage between G434A and the EBS-DM phenotype, with a LOD score of 3.29 at a recombination rate of 0%. Codon 125 substitutions identified in three unrelated sporadic EBS-DM patients were not found in their clinically unaffected parents. Together, these data provide compelling genetic evidence that the codon 125 substitutions are causal for EBS-DM. The high frequency of mutation at this site in individuals with EBS-DM now makes DNA-based diagnosis of this disorder feasible.

Keywords:

blisters, intermediate filaments, epidermolysis bullosa herpetiformis, Genodermatosis

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