Novel and very rare causative variants in the COL7A1 gene of Vietnamese patients with recessive dystrophic epidermolysis bullosa revealed by whole‐exome sequencing.

Ma, Thi Huyen Thuong; Luong, Thi Lan Anh; Hoang, Thu Lan; Nguyen, Thi Thanh Hoa; Vu, Thi Ha; Tran, Van Khoa; Nguyen, Duy Bac; Trieu, Tien Sang; Nguyen, Hai Ha; Nong, Van Hai; Nguyen, Dang Ton

Background: Dystrophic epidermolysis bullosa (DEB) is a rare inherited disorder characterized by skin fragility leading to trauma‐induced subepidermal blisters and healing with scarring. DEB is caused by mutations in COL7A1, the gene encoding for type VII collagen (COLVII). The DEB inheritance trait is divided into dominant dystrophic epidermolysis bullosa (DDEB) and recessive dystrophic epidermolysis bullosa (RDEB). Methods: Whole‐exome sequencing (WES) was performed for identifying mutations in six affected individuals of five Vietnamese families. Results: Three novel variants in total of eight variants were found in five families. The first novel variant causing glycine substitution (c.8279G>A, p.G2760E), the remaining two novel variants resulted in splice site affecting (c.4518 2delT and c.5821‐2A>G). Functional analysis indicated that the splice site at c.4518 2delT resulted in a skipping of exon 43, leading to an in‐frame deletion of 12 amino acids. Conclusion: Our finding expands the spectrum of COL7A1 mutations and reports altered splicing at c.4518 2delT during the processing of the pre‐mRNA. This study provides an additional scientific basis for diagnosis, genetic counseling, and prognosis purposes of EB patients.

EPIDERMOLYSIS bullosa; GENETIC variation; EXOMES; RECESSIVE genes; GENETIC counseling; FUNCTIONAL analysis

Molecular Genetics & Genomic Medicine, 2021, Vol 9, Issue 8, p1

2324-9269

Academic Journal

10.1002/mgg3.1748