A novel variant c.A527G in ITGB4 leads to autosomal dominant epidermolysis bullosa in China

Objective This study aimed to uncover the genetic variations and their corresponding clinical features in a Chinese family affected by epidermolysis bullosa (EB). Methods We enrolled a Chinese family clinically diagnosed with EB and conducted whole-exome sequencing on the proband to identify genetic variations. I-TASSER and PyMOL software were used to examine the structural and functional implications of the identified mutant proteins. Results The study identified an autosomal-dominant form of epidermolysis bullosa simplex (EBS) in the family, attributed to a novel missense variation c.A527G (D176G) in the ITGB4 gene. By bioinformatics analyses, we found that the wild-type D176 forms one hydrogen bond with a distance of 3.1 Å from F201, one hydrogen bond with a distance of 2.7 Å from K177, and two hydrogen bonds with a distance of 3.2 Å from Y304; however, the mutant G176 only forms one hydrogen bond with F201 at a distance of 3.2 Å. Conclusions This study confirms the dominant mode of inheritance of the missense ITGB4 mutation observed in EB. The novel missense variation c.A527G (D176G) in ITGB4 involves a transition from a polar to non-polar amino acid and a decrease in intermolecular hydrogen bonding, which was associated with EB development.