Variants in RIPOR2 gene related to hearing loss are infrequent in Northern Spain

Introduction and objective: To assess the prevalence and clinical characterization of variants in the RIPOR2 gene among patients with bilateral sensorineural hearing loss (SNHL) of unknown etiology in northern Spain. Method: This 7-year (2018–2024) observational, retrospective, and descriptive study involved patients with bilateral SNHL treated at a tertiary hospital. Genetic analysis was performed using next-generation sequencing (NGS), employing a gene panel for sensorineural hearing loss. The presence of RIPOR2 gene variants was specifically analyzed. Results: Among the 381 patients, two variants in the RIPOR2 gene were identified in three individuals (0.8 %): c.1879G>A (p.Asp627Asn) and c.3193G>A (p.Ala1065Thr). The variant c.1879G>A was detected in two patients, while the c.3193G>A variant was found in only one patient who also carried other pathogenic variants associated with hearing loss. The three patients exhibited cookie-bite hearing loss, predominantly affecting the 1000, 2000, and 4000 Hz frequencies, respectively, without associated vestibular symptoms. Conclusions: variants in the RIPOR2 gene are infrequent among patients with SNHL in northern Spain (Cantabria). Moreover, there is no conclusive evidence supporting their pathogenicity in cases of SNHL with unknown etiology. Further studies are needed to clarify their clinical significance.