The study investigated the genetic variation and clinical features of epidermolysis bullosa (EB) in a Chinese family. Whole-exome sequencing was performed on the proband to identify genetic alterations. They identified a novel missense variation c.A527G (D176G) in the ITGB4 gene that causes an autosomal dominant form of epidermolysis bullosa simplex (EBS). Through bioinformatic analyzes using I-TASSER and PyMOL software, they found that wild-type D176 forms four hydrogen bonds: one 3.1 Å from F201, one 2.7 Å from K177, and two 3.2 Å from Y304. Mutant G176 forms only one hydrogen bond with F201 at a distance of 3.2 Å. This variation changes the polar amino acid D to a nonpolar G and reduces intermolecular hydrogen bonding. The study confirms the dominant mode of inheritance of this ITGB4 mutation associated with EB.