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

## TL;DR

A new genetic mutation in the ITGB4 gene causes a form of epidermolysis bullosa in a Chinese family.

## Contribution

A novel missense mutation c.A527G (D176G) in ITGB4 is identified as a cause of autosomal dominant epidermolysis bullosa.

## Key findings

- The mutation c.A527G (D176G) in ITGB4 leads to autosomal dominant epidermolysis bullosa simplex.
- The D176G mutation reduces hydrogen bonding in the protein structure, potentially causing disease.

## Abstract

This study aimed to uncover the genetic variations and their corresponding clinical features in a Chinese family affected by epidermolysis bullosa (EB).

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.

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.

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.