# Identification of Novel USH2A Mutations in a Consanguineous Chinese Family With Usher Syndrome

## TL;DR

This study identifies new mutations in the USH2A gene in a Chinese family with Usher syndrome, a rare condition causing hearing and vision loss.

## Contribution

The paper reports novel homozygous and compound mutations in USH2A, expanding the known genetic variants associated with Usher syndrome.

## Key findings

- A novel homozygous frameshift mutation in USH2A was identified in one patient, causing a truncated protein.
- Compound mutations in USH2A were found in another patient, with in silico analysis suggesting functional disruption.
- The findings expand the spectrum of USH2A mutations and aid in genetic screening for Usher syndrome.

## Abstract

Usher syndrome (USH) is a rare genetic disease characterized by sensorineural deafness and blindness called retinitis pigmentosa, and it is inherited in an autosomal recessive pattern with a prevalence of four to 17 per 100,000 people worldwide. In this study, a consanguineous Chinese family with USH, including two affected individuals and five unaffected individuals, was recruited. All subjects received an ophthalmic examination and an auditory examination. The two USH patients exhibited severe early-onset hearing and vision loss. DNA samples from the two USH patients were analyzed using whole-exome sequencing. A novel homozygous frameshift mutation (NM_206933.4:c.6379_6380delinsC, p.G2127Pfs∗25) in USH2A, resulting in a truncated USH2A protein lacking 3051 amino acids, was identified in the proband. In addition, novel compound mutations in USH2A (one allele harboring NM_206933.4:c.9958G>T, p.G3320C; NM_206933.4:c.8284C>G, p.P2762A; and the other NM_206933.4:c.6379_6380delinsC; p.G2127Pfs∗25) were identified in the other affected individual. In silico analysis predicts that while the p.G3320C mutation has little impact on the local structure around the mutation site, the p.P2762A substitution may alter the protein's interaction with its binding partners. In addition, p.G2127Pfs∗25 causes a truncation of a major portion of the protein that severely disrupts the protein structure and results in the loss of its function. In conclusion, this study identified novel USH mutations in USH2A and expanded the spectrum of disease-associated variants in the USH2A gene, which will promote the molecular screening of genetic mutations in USH patients.