RESUMEN
BACKGROUND: Auditory Neuropathy Spectrum Disorder (ANSD) is manifested as impairment of auditory nerve activity but preservation of the outer hair cell function. OBJECTIVE: This study was to detect the disease-causing gene and variant(s) in a Chinese ANSD family. METHODS: A four-generation consanguineous Chinese ANSD family and 200 unrelated healthy controls were enrolled. Exome sequencing and Sanger sequencing were applied to identify the genetic basis for ANSD in this family. RESULTS: Exome sequencing detected a c.1236delC variant of the otoferlin gene in an apparently homozygous state. Sanger sequencing confirmed that the variant co-segregating with the phenotype of hearing impairments in this family. The variant was not detected in 200 healthy controls. The c.1236delC alteration may result in a truncated otoferlin missing the C2C-C2F domains and the C-terminal transmembrane domain, and thus severely damages Ca2+-dependent synaptic vesicle fusion and targeting function of the otoferlin. CONCLUSION: Our study suggested that the c.1236delC alteration in the otoferlin gene may be the disease-causing variant in this family, and also shed new light on genetic counseling to this ANSD family.