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

• Published in: Molecular genetics & genomic medicine Vol. 9; no. 8; pp. e1748 - n/a
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-08-2021; John Wiley and Sons Inc; Wiley
• Subjects: Amino acids; Blistering; Blisters; Cells, Cultured; Child; Child, Preschool; COL7A1; Collagen; Collagen (type VII); Collagen Type VII - genetics; Collagen Type VII - metabolism; Dystrophic epidermolysis bullosa; Epidermolysis bullosa; Epidermolysis Bullosa Dystrophica - genetics; Epidermolysis Bullosa Dystrophica - pathology; Families & family life; Female; Fingers & toes; Fragility; Functional analysis; Genetic counseling; Genetic screening; Genomes; Glycine; Heredity; Humans; Male; mRNA; Mutation; novel variants; Original; Parents & parenting; Patients; Pedigree; RNA Splicing; Scars; Splicing; Trauma; Whole Exome Sequencing; United Kingdom > UK; England; Vietnam; novel variants; whole-exome sequencing; COL7A1; dystrophic epidermolysis bullosa
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1748

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.
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). Whole‐exome sequencing (WES) was performed for identification of mutations in six affected individuals of five Vietnamese families. Three novel variants out of eight variants were found in five families.