Prevalence and spectrum of STRC variants in 1015 sensorineural hearing loss patients: insights from the Chinese...

Mutations in the STRC gene are a major cause of autosomal recessive mild-to-moderate sensorineural hearing loss (SNHL); however, its prevalence and mutational spectrum in the Chinese population remain largely unexplored. To address this, we analyzed 1015 unrelated Chinese patients with bilateral SNHL using whole-exome sequencing (WES), multiplex ligation-dependent probe amplification (MLPA), and Sanger sequencing. Biallelic STRC variants were identified in 2.1% of all patients, with the diagnostic yield significantly rising to 15.6% among mild-to-moderate SNHL cases. Copy number variants (CNVs) were predominant (90.5%, 19/21), which were potentially mediated by non-allelic homologous recombination (NAHR) involving the pseudogene STRCP1. Notably, 26.2% (11/42) of mutant alleles harbored CNVs spanning both STRC and the adjacent CATSPER2 gene, highlighting critical implications for clinical management and genetic counseling due to potential syndromic associations. MLPA detected additional CNVs missed by WES, emphasizing the necessity of combining multiple genetic testing strategies. Audiologically, patients with biallelic STRC variants exhibited a distinctive frequency-dependent hearing loss, characterized by mild impairment at low frequencies (0.125-0.5 kHz) and moderate to moderately severe impairment at higher frequencies (0.5-8 kHz). These findings highlight the critical importance of CNV detection for genetic diagnosis and clinical management of STRC-related SNHL, particularly in mild-to-moderate cases, and provide essential insights for genetic counseling involving co-occurring STRC and CATSPER2 CNVs.