Compound heterozygous mutations in the USH2A gene causing non-syndromic retinitis pigmentosa

To investigate the genetic defects underlying retinitis pigmentosa (RP) in a Chinese family.

A Chinese family with RP was recruited. Whole-exome sequencing was conducted to identify potential pathogenic variants, and Sanger sequencing was used for validation. Segregation analysis was performed among family members, and bioinformatics tools were employed to predict the functional impact of the identified mutations.

The proband's primary ocular findings included attenuated arterioles, waxy pallor of the optic disc, peripheral bone-spicule pigmentation, and diffuse choroidal atrophy. Whole-exome sequencing and Sanger sequencing revealed two heterozygous mutations in the USH2A gene: c.8641_8642insTATT (p.Ser2881LeufsX9) and c.10721 G > A (p.Gly3574Asp). The frameshift mutation has been reported previously, while the missense mutation is extremely rare and has not previously been associated with any known phenotype. Functional predictions from multiple bioinformatics tools suggested both mutations are likely pathogenic. Evolutionary conservation analysis indicated that the Ser2881 and Gly3574 residues are highly conserved across species. Although the p.Gly3574Asp mutation did not significantly alter the protein's secondary structure, it introduced changes in charge and hydrophobic interactions.

We identified compound heterozygous mutations in USH2A in a Chinese family with RP. Our findings expand the known mutation spectrum of USH2A and contribute to a better understanding of the genetic basis of RP.