Genetic diagnosis of a rare COL7A1 variant causing dystrophic epidermolysis bullosa pruriginosa through whole‑exome sequencing

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of inherited DEB. In the present study, whole-exome sequencing was conducted on 12 individuals from the same affected family and a rare heterozygous variation was identified in the collagen type VII, α1 (COL7A1) gene, namely c.6859G>A (p.Gly2287Arg). Subsequently, this heterozygous variant was confirmed using Sanger sequencing of individual plasma cell-free DNA (cfDNA) and it was demonstrated for the first time, to the best of our knowledge, that COL7A1 exons can be amplified from plasma cfDNA. Within the large pedigree examined, 14 out of 18 individuals carried the variant, 3 carried the wild type, and one exceptional case, III-9, showed no disease symptoms despite carrying the disease variant. A general association between genotype and phenotype was established. Of note, the mutation landscape indicated that this G2287R variant is primarily reported in Asian countries. In silico structure prediction suggested that the residue resulting from the mutation may affect collagen protein stability. In conclusion, the present study provides evidence for the involvement of the COL7A1 G2287R gene variant in the development of DEB-Pr and highlights the potential utility of cfDNA in genetic disease diagnosis.