Xiang Yanbao, Li Huanzheng, Xu Xueqin, Xu Chenyang, Chen Chong, Lin Xiaoling, Tang Shaohua
Key Laboratory for Birth Defect of Weazhou City, Central Laboratory, Central Hospital of Wenzhou, Wenzhou, Zhejiang 325000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2017 Jun 10;34(3):336-341. doi: 10.3760/cma.j.issn.1003-9406.2017.03.005.
To carry out mutation analysis and prenatal diagnosis for 12 families affected with hearing loss and enlarged vestibular aqueduct from southern Zhejiang province.
Clinical data and peripheral venous blood samples of 38 members from the 12 families were obtained. Mutations of 4 genes, namely SLC26A4, GJB2, c.538C to T and c.547G to A of GJB3, m.1555A to G and m.1494C to T of 12S rRNA, were detected by PCR and Sanger sequencing. Maternal contamination was excluded by application of STR detection during prenatal diagnosis.
Among the probands from the 12 families, 11 were found to be compound heterozygotes or homozygotes and 25 were heterozygotes. All of the families were detected with IVS7-2A to G mutations, and 4 had a second heterozygous mutation (c.2168A to G of the SLC26A4 gene). Four rare pathogenic mutations, namely IVS5-1G to A, c.946G to T, c.1607A to G and c.2167C to G, were detected in another four families. In addition, the partner of proband from pedigree 3 was identified with compound heterozygous mutations of c.235delC and c.299-300delAT, and proband of pedigree 5 has carried a mutation of c.109G to A in GJB2. For SLC26A4 gene, prenatal diagnostic testing has revealed heterozygous mutations in 6 fetuses and compound heterozygous mutations in 2 fetuses.
IVS7-2A to G and c.2168A to G of the SLC26A4 gene were the most common mutations in southern Zhejiang. Such mutations can be found in most families affected with hearing loss and enlarged vestibular aqueduct, which may facilitate genetic counseling and prenatal diagnosis for such families.
对来自浙江南部的12个患有听力损失和前庭导水管扩大的家庭进行突变分析和产前诊断。
获取这12个家庭中38名成员的临床资料和外周静脉血样本。通过聚合酶链反应（PCR）和桑格测序检测4个基因的突变，即SLC26A4、GJB2、GJB3基因的c.538C突变为T和c.547G突变为A、12S rRNA的m.1555A突变为G和m.1494C突变为T。在产前诊断期间应用短串联重复序列（STR）检测排除母体污染。
在这12个家庭的先证者中，11例为复合杂合子或纯合子，25例为杂合子。所有家庭均检测到IVS7-2A突变为G的突变，4个家庭有第二个杂合突变（SLC26A4基因的c.2168A突变为G）。在另外4个家庭中检测到4种罕见的致病突变，即IVS5-1G突变为A、c.946G突变为T、c.1607A突变为G和c.2167C突变为G。此外，家系3的先证者配偶被鉴定为c.235delC和c.299-300delAT的复合杂合突变，家系5的先证者携带GJB2基因的c.109G突变为A的突变。对于SLC26A4基因，产前诊断检测显示6例胎儿为杂合突变，2例胎儿为复合杂合突变。
SLC26A4基因的IVS7-2A突变为G和c.2168A突变为G是浙江南部最常见的突变。此类突变在大多数患有听力损失和前庭导水管扩大的家庭中均可发现，这可能有助于对此类家庭进行遗传咨询和产前诊断。
