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

https://doi.org/10.1111/1523-1747.ep12365079Get rights and content
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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 often 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.

blisters
intermediate filaments
epidermolysis bullosa herpetiformis
Genodermatosis

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