Dominant dystrophic epidermolysis bullosa with COL7A1 variant confirmed by whole-exome sequencing in a Chinese family and genotype-phenotype correlation analysis

Introduction: Epidermolysis Bullosa (EB) comprises a diverse group of rare, incurable genetic disorders characterized by blistering of the skin. These conditions have variable clinical presentations and poorly understood genotypes and phenotypes. This study aims to confirm the diagnosis of dystrophic epidermolysis bullosa (DEB) in a family and analyze gene-phenotype correlations. Methods: The study involved three patients, two controls, and one member with unknown phenotype. We performed whole exome sequencing (WES) on two family members to identify EB-associated genes, with Sanger sequencing for validation. Results: 1) WES revealed missense variants in the COL7A1 ([c.4274T>C.L1425P] and [c.3602G>A.R1201H]) genes in the family, although recorded in the dbSNP database, they have not been reported in previous articles, and classified as of uncertain significance by InterVar. These findings were confirmed by Sanger sequencing. 2) Statistical analysis indicated a significant association between dystrophic epidermolysis bullosa and epidermolysis bullosa simplex (EBS) with junctional epidermolysis bullosa (JEB) (P=0.031) in dominant and recessive inheritance patterns, respectively. However, no significant correlation was found between the clinical phenotype of DEB and variant types (nonsense and missense), inheritance patterns (dominant and recessive), or between familial and sporadic cases. Conclusion: This study identified variants in the COL7A1 gene within Chinese families, expanding the variant spectrum of DEB. These findings lay the groundwork for improved genetic diagnosis and counseling.