2.1. Subjects and Clinical Assessments

The proband (Figure 1(a), IV-1) with bilateral profound sensorineural hearing loss was enrolled through the Department of Otorhinolaryngology at Shanghai Ninth People's Hospital. Four other subjects (II1-1, II1-2, II-1, and II-2) from the four-generation family and 100 Chinese Han normal hearing controls were also included in this study. The clinical evaluation included a detailed medical history questionnaire and a thorough physical examination. Auditory evaluations were performed in all participants, including otoscopic examination, otoacoustic emissions (OAEs), auditory evoked potentials (AEPs), or pure-tone audiometry. High-resolution computerized tomography (CT) scan of the temporal bone was performed in proband IV-1. Sense of smell was evaluated by self-report, questioning, or olfactory tests. Blood sample was collected from the proband and her family members, and total DNA was extracted from peripheral blood leukocytes using standard protocols.

Pedigree of the family and clinical findings of the proband IV-1: (a) pedigree and genotype showing the c.481C>T (p.R161C) mutation in SOX10 and the c.235delC (p.L79Cfs∗3) mutation in GJB2; (b) auditory evoked potentials showing bilateral profound sensorineural hearing loss.