OSBPL2-related autosomal dominant hearing loss: a family analysis and literature review.

Chinese families with hearing loss definitively attributed to OSBPL2 gene variation via whole-exome sequencing at the Molecular Diagnostic Center for Hereditary Hearing Loss, PLA General Hospital from June 2022 to February 2025 were retrospectively analyzed. Meanwhile, a review of OSBPL2-related deafness literature from PubMed and CNKI databases (2014-2025) was performed to analyze the genotype and phenotype of OSBPL2 gene. Among 607 families with deafness, there was only one (0.16%) novel de novo frameshift variation (affecting amino acid 53, p.Gln53), presenting with bilateral, symmetric, late-onset, progressive sensorineural hearing loss starting with high frequencies during late adolescence and gradually involving all frequencies. This patient demonstrated high consistency in genotype and phenotype with six previously reported families and one sporadic case. The current findings reveal that OSBPL2 variants-caused autosomal dominant nonsyndromic hearing loss 67 (DFNA67) is rare, predominantly frameshift variations, and can occur de novo, with p.Gln53 as a mutation hotspot. Therefore, for individuals with progressive sensorineural hearing loss starting with high frequencies and having relatively uniform phenotype, genetic testing for OSBPL2 should be considered.