# Clinical and Allelic Heterogeneity in a Small Cohort of Patients with Inherited Epidermolysis Bullosa

## TL;DR

This study uses whole-exome sequencing to identify genetic mutations in a small group of patients with inherited epidermolysis bullosa, a skin disorder, and finds new mutations that could help improve diagnosis and treatment.

## Contribution

The study identifies four novel COL7A1 mutations and demonstrates the utility of whole-exome sequencing in diagnosing epidermolysis bullosa.

## Key findings

- Whole-exome sequencing identified four novel COL7A1 mutations and other variants in EB patients.
- In silico tools suggested splicing disruption in KRT5 and LAMB3 mutations.
- Topical gentamicin therapy was used to target a nonsense mutation in one patient.

## Abstract

Inherited epidermolysis bullosa (EB) comprises a group of genetic disorders characterized by fragile skin that blisters easily. Targeted therapies for EB necessitate personalized approaches, underscoring the importance of precise diagnostics through genetic analysis and skin biopsy using transmission electron microscopy and/or immunohistochemistry. This study highlights the application of whole-exome sequencing (WES) to identify key pathogenic variants associated with EB. Most identified variants were associated with the recessive form of dystrophic EB, including four novel COL7A1 mutations: p.Leu1488ArgfsTer222, c.7759-3C>G, p.Gln1886Ter, and c.6501+6T>C, as well as recurrent variants p.Lys142Arg and p.Gly2049Glu. Additionally, variants were detected in KRT5 (c.971T>C, p.Val324Ala), associated with EB simplex, and in LAMB3 (c.2500C>T, p.Gln834Ter) in the homozygous state, associated with junctional EB. In silico splice prediction tools suggested disrupted splicing in both cases. One patient received topical gentamicin therapy targeting the nonsense mutation p.Gln1886Ter. These findings underscore the utility of WES in EB diagnostics, broaden the mutation spectrum, and contribute to the understanding of genotype–phenotype correlations in adult patients with EB.