Analysis of COL7A1 pathogenic variants in a large cohort of dystrophic epidermolysis bullosa patients from Argentina reveals a new genotype–phenotype correlation

Abstract

Dystrophic epidermolysis bullosa (DEB) is a clinically heterogeneous heritable skin disorder, characterized by blistering of the skin and mucous membranes following minor trauma. Dominant (DDEB) and recessive (RDEB) forms are caused by pathogenic variants in COL7A1 gene. Argentina's population has a heterogeneous genetic background, and little is known about the molecular basis of DEB in our country or in native South American populations. In this study, we present the prevalence and geographical distribution of pathogenic variants found in 181 patients from 136 unrelated families (31 DDEB and 105 RDEB). We detected 95 different variants, 59 of them were previously reported in the literature and 36 were novel, nine of which were detected in more than one family. The most prevalent pathogenic variants were identified in exon 73 in DDEB patients and in exon 3 in RDEB patients. We also report a new phenotype–genotype correlation found in 10 unrelated families presenting mild blistering and severe mucosal involvement. Molecular studies in populations with an unexplored genetic background like ours revealed a diversity of pathogenic variants, and we hope that these findings will contribute to the definition of targets for new gene therapies.

A case of adult‐onset localized recessive dystrophic epidermolysis bullosa, harboring the novel COL7A1 mutation p.G2754E and the previously reported mutation p.R1763*

“…In contrast, 26.3% of Argentinian and 33.3% of Brazilian RDEB patients had a localized subtype, implying that the subtype is common in Latin America. 3,4 Although unique variants for localized RDEB have not been reported so far, c.7380 + 2 T > C was the most prevalent pathogenic variant among patients with the localized subtype in Argentina. Interestingly, localized RDEB often lacks early clinical signs of RDEB and presents only in later life, 5 which is consistent with the history of our patient.…”

Junctional epidermolysis bullosa: genotype-phenotype correlations

“…В дебюте заболевания, который обычно приходится на младенческий возраст, опираясь только лишь на клинические данные прогнозировать дальнейшее течение болезни невозможно. Тем не менее, предполагается, что анализ клинико-генетических корреляций позволит определить течение различных субтипов врожденного буллезного эпидермолиза, так как клинические проявления заболеваний определяются геном, в котором произошла мутация, влиянием патогенной мутации на синтез белка и локализацией мутантного белка, который может экспрессироваться в различных органах и тканях помимо кожи [8,9].…”