中文摘要：

目的：分析大前庭水管综合征（large vestibular aqueduct syndrome，LVAS）患者家系的SLC26A4基因突变方式并确定其是否致病。方法采集3个特殊LVAS家系的血样，测序分析SLC26A4基因型。采用在线软件SIFT、Polyphen-2预测这3个家系中所携带的罕见突变方式的致病性，利用排除法证明c.2343＋69C＞A的非致病性。结果共检出5种突变方式，其中4种为致病性基因突变。先证者基因型为IVS7-2A＞G/c.1594A＞C，IVS7-2A＞G/c.1327G＞C，IVS7-2A＞G/c.1667A＞G，均为LVAS。基因型为c.1594A＞C/2343＋69C＞A，c.1327G＞C/c.2343＋69C＞A，c.1667A＞G/c.2343＋69C＞A的受检者听力正常。结论 SLC26A4基因c.2343＋69C＞A突变方式是非致病的基因多态；3个家系先证者的父母再次妊娠出现聋儿的风险为25％。

英文摘要：

Objective To sequence and analyze the pathogenesis of the mutation of SLC26A4 gene in 3 families of LVAS.Methods Blood samples and clinical data of 3 families of LVAS were collected. A pathogenesis analysis was conducted on the rare genemutation in the families using online software. Using a process of elimination to prove that c.2343＋69C〉A is benign.Results We detected five SLC26A4 gene mutations from 3 families, and confirmed that four mutations out of them are pathogenic.The genotypes of IVS7-2A〉G/c.1594A〉C, IVS7-2A〉G/c.1327G〉C, IVS7-2A〉G/c.1667A〉G are the probands. The genotypes of c.1594A〉C/c.2343＋69C〉A,c.1327G〉C/c.2343＋69C〉A, c.1667A〉G/c.2343＋69C〉A case have normal hearing.Conclusion According to our results, SLC26A4 c.2343＋69C〉A is not likely to be a pathogenic mutation.If the parents of any proband of these three families want to rebirth, the newborn might have 25 percent chance to be with EVAS as the proband.