An OTOF Frameshift Variant Associated with Auditory Neuropathy Spectrum Disorder

作者：Xia, Hong; Huang, Xiangjun; Xu, Hongbo; Guo, Yi; Hu, Pengzhi; Deng, Xiong; Yang, Zhijian; Liu, An; Deng, Hao^*

来源：Current Genomics, 2018, 19(5): 370-374.

DOI：10.2174/1389202919666171113152951

• Auditory neuropathy spectrum disorder
• Exome seq uencing
• Hearing loss
• Variant
• The OTOF gene
• ANSD family

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.

• 出版日期2018
• 单位湖南中医药大学; 中南大学