西藏地区Waardenburg综合征患者基因突变及人工耳蜗植入术后听觉言语康复效果分析

Gene Variant Analysis of Patients with Waardenburg Syndrome in Tibet and the Effect of Hearing and Speech Rehabilitation after Cochlear Implantation

目的分析中国西藏地区一Waardenburg综合征家系的临床特征及致病基因,总结Waardenburg综合征患者人工耳蜗植入术后听觉言语康复效果。方法采集该家系成员的病史、体格检查、听力及影像学等临床资料,利用已知耳聋基因目标区域高通量测序和Sanger测序验证,进行耳聋致病基因分析与鉴定。通过电话随访调查患者人工耳蜗术后听觉言语康复效果,使用量表包括听觉行为分级(CAP)、言语可懂度分级(SIR)、有意义听觉整合量表(MAIS)、有意义言语使用量表(meaningful use of speech scale,MUSS)。结合文献回顾,分析Waardenburg综合征患者人工耳蜗术后康复效果。结果该患儿表现为重度感音神经性耳聋,伴虹膜异色,皮肤异常,诊断为II型Waardenburg综合征。高通量测序及Sanger测序验证结果显示患儿携带SOX10基因c.409Adel杂合突变,患儿父母均未携带此突变,考虑为基因突变导致,该突变此前尚未报道。患儿人工耳蜗术后9年听觉言语康复效果良好,CAP、SIR分级分别为6级、4级,MAIS、MUSS评分分别为37分、32分。结论本研究发现1例西藏地区II型Waardenburg综合征患者新发SOX10基因突变位点c.409Adel,丰富了中国藏族人群致聋基因突变谱。Waardenburg综合征患者人工耳蜗术后远期听觉言语康复效果满意。

Objective To analyze the clinical features and pathogenic genes variant of a family of Waardenburg syndrome in Tibet,China,and review relevant literatures to summarize the effects of hearing and speech rehabilitation in patients with Waardenburg syndrome after cochlear implantation.Methods The medical history,physical examination,hearing,imaging and other clinical data of the family members were collected in detail,and the disease-causing genes of deafness were analyzed and identified by high-throughput sequencing and Sanger sequencing.The effect of hearing and speech rehabilitation after cochlear implantation was investigated by telephone follow-up.The methods include Categories of Auditory Performance(CAP)and Speech Intelligibility Rating(SIR),the Meaningful Auditory Integration Scale(MAIS)and the Meaningful Use of Speech Scale(MUSS).Based on the literature review,the rehabilitation effect of postoperative cochlear implantation in patients with Waardenburg syndrome was analyzed.Results The child presented with severe sensorineural deafness accompanied by heterochromia of iris and abnormal skin,and was diagnosed as Waardenburg syndrome type II.High-throughput sequencing and Sanger sequencing confirmed that the child carried a heterozygotic variant of SOX10 gene c.409Adel,and neither of the child's parents carried this variant,which was considered to be caused by a genetic variant.This had not been reported before.9 years after cochlear implantation,the child had good hearing and speech rehabilitation results.The CAP and SIR Grades were 6 and 4 respectively,and the MAIS and MUSS scores were 37 and 32 respectively.Conclusion This study found a novel SOX10 gene variant site c.409Adel in a patient with type II Waardenburg syndrome in Tibet,which enriched the genetic variant spectrum of deafness in Tibetan population in China.Patients with Waardenburg syndrome had satisfactory hearing and speech rehabilitation after cochlear implantation in long-term.