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 Cterminal
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 diseasecausing
variant in this family, and also shed new light on genetic counseling to this ANSD family.