Yuan Yong-yi, Dai Pu, Zhu Qing-wen, Kang Dong-yang, Huang De-liang
Department of Otorhinolaryngology Head and Neck Surgery, General Hospital of People's Liberation Army, Beijing 100853, China.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2009 Jun;44(6):449-54.
To investigate the whole sequence of SLC26A4 gene among 1552 deaf students from 21 regions of China with SLC26A4 hot spot mutation IVS7-2A > G and analyze the epidemiological state of enlarged-vestibular-aqueduct-syndrome (EVAS) related hearing loss in China.
DNA was extracted from peripheral blood of 1552 students from deaf and dumb school of 21 regions in China. The nationality of the 1552 cases covers Han (1290 cases), Uigur (69 cases), Hui (37 cases), Mongolia (31 cases), Yi, Zhuang, Bai, Miao and other 13 nationalities (125 cases). Firstly, all subjects were analyzed for the hot spot mutation IVS7-2A > G by direct sequencing. Those carrying a single heterozygous IVS7-2A > G were given further analyzed for the probable second mutation in other exons except exon7 and exon8 of SLC26A4. One hundred and fifty cases with normal hearing were in the control group.
The sequencing results revealed 197 cases carrying IVS7-2A > G, of whom 83 carrying IVS7-2A > G homozygous mutation, 114 carrying IVS7-2A > G heterozygous mutation. Of the 114 cases with heterozygous IVS7-2A > G, 78 cases were found to have another mutation and 36 cases were found no other mutation in SLC26A4. Of the 1552 cases, the percentage of cases carrying homozygous IVS7-2A > G and compound heterozygous mutations was 10.37% (161/1552). Of the 78 cases with SLC26A4 compound heterozygous mutations, the mutations except IVS7-2A > G were found mainly in exon 19, 10, 17, 15, 11 + 12, 14 and 3. Twenty-one novel SLC26A4 mutations were found. In the control group, there were only 3 cases carrying heterozygous IVS7-2A > G, and no other mutation in SLC26A4 was found.
SLC26A4 mutations account for at least 10% of EVAS related hereditary hearing loss in China. It's of great importance to screen SLC26A4 gene for making aetiological diagnosis for deafness. The discovery of novel variants of SLC26A4 gene makes the mutational and polymorphic spectrum more plentiful in Chinese population. We also provide preliminary evidence for the hot spot areas of SLC26A4.
对来自中国21个地区的1552名携带SLC26A4基因热点突变IVS7-2A＞G的聋校学生进行SLC26A4基因全序列分析，分析中国大前庭导水管综合征（EVAS）相关听力损失的流行病学状况。
采集来自中国21个地区聋哑学校1552名学生的外周血提取DNA。1552例患者的民族涵盖汉族（1290例）、维吾尔族（69例）、回族（37例）、蒙古族（31例）、彝族、壮族、白族、苗族等13个民族（125例）。首先，采用直接测序法对所有研究对象进行热点突变IVS7-2A＞G分析。对携带单个杂合IVS7-2A＞G的患者进一步分析SLC26A4基因除第7和第8外显子外其他外显子可能存在的第二个突变。选取150例听力正常者作为对照组。
测序结果显示携带IVS7-2A＞G者197例，其中83例为IVS7-2A＞G纯合突变，114例为IVS7-2A＞G杂合突变。在114例IVS7-2A＞G杂合突变患者中，78例发现存在另一个突变，36例未发现SLC26A4基因其他突变。1552例患者中，携带IVS7-2A＞G纯合突变和复合杂合突变的比例为10.37%（161/1552）。在78例SLC26A4基因复合杂合突变患者中，除IVS7-2A＞G外的突变主要分布在第19、10、17、15、11+12、14和3外显子。发现21个新的SLC26A4基因突变。对照组仅3例携带IVS7-2A＞G杂合突变，未发现SLC26A4基因其他突变。
SLC26A4基因突变至少占中国EVAS相关遗传性听力损失的10%。筛查SLC26A4基因对耳聋病因诊断具有重要意义。SLC26A4基因新变异的发现使中国人群的突变和多态性谱更加丰富。我们也为SLC26A4基因的热点区域提供了初步证据。
