Chen Dong-Ye, Chai Yong-Chuan, Yang Tao, Wu Hao
Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Ear Institute, Shanghai Jiaotong University, Shanghai 200092, China.
Int J Pediatr Otorhinolaryngol. 2013 Oct;77(10):1711-5. doi: 10.1016/j.ijporl.2013.07.031. Epub 2013 Aug 9.
To characterize the clinical features of a Chinese DFNA9 family associated with a novel COCH mutation and to confirm the proposed genotype-phenotype correlation of COCH.
Mutation screening of 79 deafness genes was performed in the proband by targeted next-generation sequencing. Co-segregation of the disease phenotype and the detected variants was confirmed in all family members by PCR amplification and Sanger sequencing. The progression of hearing impairment in affected family members was followed and the concomitant vestibular dysfunction was verified by the caloric vestibulo-ocular reflex test.
A novel COCH mutation p.G87V was identified in the family segregating with late-onset, progressive sensorineural hearing impairment and consistent vestibular dysfunction.
The p.G87V mutation leads to a very similar phenotype as a previously reported p.G87W mutation of COCH. Our study suggested that the G87 residue is critical for function of COCH and further confirms a previously proposed genotype-phenotype correlation for DFNA9.
对一个与新型COCH突变相关的中国DFNA9家系的临床特征进行描述，并确认所提出的COCH基因的基因型-表型相关性。
通过靶向二代测序对先证者进行79个耳聋基因的突变筛查。通过PCR扩增和桑格测序在所有家庭成员中确认疾病表型与检测到的变异的共分离情况。对受影响家庭成员的听力减退进展情况进行随访，并通过冷热试验前庭眼反射测试验证伴随的前庭功能障碍。
在该家系中鉴定出一种新型的COCH突变p.G87V，其与迟发性、进行性感音神经性听力减退和一致的前庭功能障碍相关。
p.G87V突变导致的表型与先前报道的COCH基因p.G87W突变非常相似。我们的研究表明，G87残基对COCH的功能至关重要，并进一步证实了先前提出的DFNA9的基因型-表型相关性。
