Somatic mosaicism for the COL7A1 mutation p.Gly2034Arg in the unaffected mother of a patient with dystrophic epidermolysis bullosa pruriginosa.

[dystrophic epidermolysis bullosa]

Dystrophic epidermolysis bullosa (DEB ) is a heritable blistering disorder caused by mutations in the type VII collagen gene , COL 7 A 1 . Although revertant mosaicism is well known in DEB , 'forward ' somatic mosaicism , in which a pathogenic mutation arises on a wild-type background , extending beyond the germ cells has not been reported . It is therefore unknown what proportion of sporadic dominant DEB (DDEB ) cases results from de novo mutations or somatic mosaic parents . In the clinically unaffected mother of a patient with DDEB-pruriginosa due to the p .Gly 2034 A rg mutation , we identified the p .Gly 2034 A rg mutation in a proportion of lymphocytes and skin cells (mutational load 10 -25 %). Our data emphasize that forward mosaicism occurs in DDEB and highlight that mutation analysis should always be performed in the parents of sporadic DDEB patients to confirm the de novo status of the mutation . This will ultimately reveal the frequency of true de novo mutations and somatic mosaicism in parents , which has important implications for genetic counselling . Our data indicate that the threshold of mutant type VII procollagen to develop DDEB must be higher than 10 -25 %, which provides a rationale for therapeutic approaches aimed at increasing the wild-type :mutant type VII collagen ratio . This article is protected by copyright . All rights reserved .

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Diseases presenting "extending beyond the germ cells has not been reported" symptom

dystrophic epidermolysis bullosa

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