A KERATIN-14 MUTATIONAL HOT-SPOT FOR EPIDERMOLYSIS-BULLOSA SIMPLEX, DOWLING-MEARA - IMPLICATIONS FOR DIAGNOSIS

被引:70
作者
STEPHENS, K
SYBERT, VP
WIJSMAN, EM
EHRLICH, P
SPENCER, A
机构
[1] UNIV WASHINGTON,DEPT MED,DIV DERMATOL,SEATTLE,WA 98195
[2] UNIV WASHINGTON,DEPT PEDIAT,SEATTLE,WA 98195
[3] UNIV WASHINGTON,CHILDRENS ORTHOPED HOSP & MED CTR,SEATTLE,WA 98105
[4] UNIV WASHINGTON,CHILDRENS ORTHOPED HOSP & MED CTR,DEPT BIOSTAT,SEATTLE,WA 98105
关键词
GENODERMATOSIS; BLISTERS; INTERMEDIATE FILAMENTS; EPIDERMOLYSIS BULLOSA HERPETIFORMIS;
D O I
10.1111/1523-1747.ep12365079
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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 G --> A substitution at base pair 434 of codon 125, whereas one case out of ten had a C --> T 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.
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页码:240 / 243
页数:4
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