[Hearing phenotype of non-syndromic hearing loss caused by variants with different pathogenicity]

The data of 14 patients with hearing loss and subjected to whole exome sequencing in Department of Otorhinolaryngology, Eye ENT Hospital, Fudan University between March 2024 and March 2025 were retrospectively analyzed. The patients were categorized into two groups: the pathogenic (P)/likely pathogenic (LP) group and the variant of uncertain significance (VUS) group. The P/LP group consisted of eight cases (three males and five females), while the VUS group included six cases (four males and two females). The median (Q₁, Q₃) age of onset in the P/LP group was significantly younger than that in the VUS group [9.0 (5.8, 12.0) years vs 27.5 (17.0, 33.3) years, P=0.014]. Hearing loss in the P/LP group was more severe than in the VUS group at specific frequencies, including 250 Hz (P=0.015), 500 Hz (P=0.023), and low frequencies (125-500 Hz, P=0.029). Hearing loss in the P/LP group was mainly sloping (9/16 ears), while in the VUS group it was either sloping (4/12 ears) or U-shaped (4/12 ears). The results suggest that early-onset, low-frequency sloping hearing loss is more likely associated with P/LP variants.