广东省59例大前庭水管综合征患者SLC26 A4基因突变及表型分析

目的：探讨广东省大前庭水管综合征（enlargement of vestibular aqueduct syndrome，EVAS）患者SLC26 A4基因位点突变及相关听力表型，为研究 EVAS 发病机制提供参考。方法采用基因芯片法对59例EVAS患儿进行 SLC26 A4基因 IVS7－2 A＞G：2168 A＞G 位点检测，并行颞骨 CT 影像学检查。结果59例EVAS患者中21例（35．59％）为SLC26 A4双等位基因（纯合或复合杂合）突变，其中16例为IVS7－2 A＞G纯合突变，2例为2168A＞G纯合突变，3例为IVS7－2A＞G、2168A＞G复合杂合突变，这21例CT均显示为双侧前庭水管扩大或其他内耳畸形；38例为 SLC26 A4单等位基因突变，其中31例为 IVS7－2 A＞G 杂合突变，7例为2168A＞G杂合突变，这38例中4例为前庭水管扩大伴Mondini畸形，2例表型正常，其余均为双侧前庭水管扩大。59例患儿均表现为重度－极重度聋。结论本组EVAS患者中SLC26 A4基因IVS7－2 A＞G位点的突变发生率最高，其次为2168A＞G；均表现为双耳重度或极重度感音神经性听力损失。

Mutations in SLC26A4 Gene and Relevant Phenotype Analysis in Fifty-nine Cases of Enlargement of Vestibular Aqueduct(EVA)Syndrome Children in Guangdong District

Objective The molecular etiology of hearing impairment in Guangdong District has not been thor-oughly investigated.SCL26A4 gene mutation and relevant phenotype were analyzed in this study.Methods The coding exons of SLC26A4 were analyzed in 59 EVA cases.Those SLC26A4 gene mutations patients were examined by temporal bone CT.Results Fifty-nine cases were SLC26A4 mutations deafness patients,and 21 cases (35. 59%)and 38 cases (64.41%)patients with SLC26A4 biallelic allele (compound homozygous or heterozygous)and monoallelic gene mutation,including 16 cases of SLC26A4 gene IVS7-2 A> G homozygous mutations,2 cases of 2168A>G homozygous mutations and 3 cases of IVS7-2A>G,2168 A > G compound heterozygous mutations in children with CT showing bilateral enlarged vestibular aqueduct or other types of inner ear malformations.Thirty-one patients were IVS7-2A>G heterozygous for SLC26A4 mutation and seven 2168 A > G heterozygous muta-tion.Four patients with SLC26A4 gene mutations were confirmed to have enlarged vestibular aqueduct with Mondini dysplasia.Two patients with normal phenotype ,and others were enlarged vestibular aqueduct.Conclusion Muta-tions in the SLC26A4 gene with enlarged vestibular aqueduct patients were frequently found in Guangdong District.IVS7-2A>G mutations rate were highest,followed by 2168 A > G.We established the new strategy that detects SLC26A4 mutations prior to the temporal bone CT scan to find enlarged vestibular aqueduct and inner ear malforma-tion patients .