国人前庭水管扩大患者SLC26A4基因的特异性突变

Specificity of SLC26A4 Mutations in Chinese Patients with Enlarged Vestibular Aqueduct

目的探讨SLC26A4基因与前庭水管扩大(enlarged vestibular aqueduct,EVA)的关系及其在中国人群EVA患者中突变的频率及分布情况,为相关基因的筛查及临床应用奠定基础。方法采集中国人群中的38例EVA核心家系,提取基因组DNA,应用聚合酶链反应(PCR)的方法扩增SLC26A4基因的21个外显子,纯化PCR产物后直接测序,使用DNAStar及Bioedit序列比对软件分析SLC26A4基因的突变位点。结果35例EVA核心家系的SLC26A4基因发生了突变,所占比例约为92.1%(35/38)。在发现的12种突变类型中,6种为新的突变类型(待发表),其余类型国际上已见报道:分别为IVS7-2A>G、L676Q、H723R、IVS15+5G>A、R409H和M147V。在所有的突变中,IVS7-2A>G突变的发生率最高,约为81.6%(31/38)。结论中国人群的EVA患者中存在SLC26A4基因的多种突变类型,其中IVS7-2A>G突变的发生率最高(81.6%),应视为特异性热点突变,建议在中国人群进行SLC26A4基因的突变热点的普遍筛查,降低EVA患儿的出生率。

Objective To investigate the contribution of SLC26A4 mutation to the Chinese patients with enlarged vestibular aqueduct（EVA） for the purpose of collection basic information for clinical application and screening. Methods A total of 38 nuclear families with EVA participated in the current study. The genomic DNA was exatracted from peripheral blood. All 21 exons of the SLC26A4 gene were amplified by intronic polymerase chain reaction（PCR）, then the PCR products were purified and directly sequenced. The sequences were analysed with DNAStar or Bioedit. Results In the present study, causative mutations were identified in 35 families. A total of 12 pathologic mutations were detected with 6 novel mutations（ data unpublished） and 6 mutations being WS7 - 2A 〉 G, L676Q, H723R, IVS15 ＋ 5G 〉 A, R409H and MI47V. In these mutations, the most common mutation was IVS7 - 2A 〉 G, identified in 81.6% of all the families. Conclusion Many different mutations in SLC26A4 gene are responsible for the deafness with EVA in Chinese population. Agressive screening of SLC26A4 gene to this mutation can reduce the birthrate of infant with enlarged vestibular aqueduct.