Abstract: Objective: To determine the prevalence of variants in the DIAPH1 gene among patients with bilateral sensorineural hearing loss of unknown etiology in northern Spain and to characterize the associated phenotype. As a secondary objective, this study aims to improve genetic counseling by linking genotype to phenotype through clinical characterization of variant carriers. Patients and methods: A six-year observational descriptive study was conducted at a tertiary referral center. Patients with bilateral sensorineural hearing loss of unknown origin were evaluated using DNA sequencing through next-generation sequencing. A gene panel was utilized to identify pathogenic or likely pathogenic variants in the DIAPH1 gene. Results: Among 385 patients with SNHL, four (1%) harbored DIAPH1 variants. Two patients (0.5%) had pathogenic or likely pathogenic variants associated with macrothrombocytopenia and neutropenia (c.3586dupA, c.3575-3C > G), exhibiting early-onset, progressive bilateral SNHL, and vestibular abnormalities. One received a cochlear implant with good outcomes. Conclusions: Pathogenic variants in the DIAPH1 gene are rare among patients with bilateral sensorineural hearing loss of unknown etiology in northern Spain. These variants lead to bilateral SNHL with autosomal dominant inheritance. In our study, we identified two novel pathogenic DIAPH1 variants associated with macrothrombocytopenia, and also presenting neutropenia and vestibular involvement. © 2025 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello
