1552例中重度感音神经性聋患者SLC26A4基因外显子7和8序列测定及热点突变分析

目的 调查全国21个地区聋哑学生SLC26A4基因热点突变及其发病频率,由此分析和推测中国人大前庭水管综合征的流行病学状况。方法调查对象来自全国21个省市自治区的聋哑学校学生1552例,其中汉族1290人,维吾尔族69人,回族37人,蒙古族31人,其他125人来自彝族、壮族、白族、苗族等18个民族,所有受检患者均采集外周血并提取DNA,以序列分析方法检测SLC26A4基因IVS7~A〉G突变及其他位点突变情况。结果 SLC26A4基因外显子7＋8序列分析结果显示1552例来自全国各地的耳聋患者中199例携带外显子7＋8及内含子7的突变,其中83例携带IVS7-2A〉G纯合突变,114例携带IVS7-2A〉G杂合突变,另有2人分别携带此区域内的其他位点突变;IVS7-2A〉G总检出率达到12．7％（197／1552）,其中1290例汉族患者中IVS7-2A〉G检出率达到14．3％,69例维吾尔族患者群中IVS7-2A〉G检出率为0。河北涿州高碑店、河南安阳患者群中的IVS7-2A〉G检出率均明显高于全国平均水平。结论通过SLC26A4基因热点突变的筛查发现在中国由SLC26A4基因突变引起的遗传性耳聋比例较高,揭示SLC26A4基因筛查和诊断在耳聋的病因学诊断中将起重要作用,并且在大规模耳聋患者的病因学筛查方面具有一定的优势。

Sequencing of SLC26A4 exons 7 and 8 and hot spot mutation analysis in 1552 moderate to profound sensorineural hearing loss patients in China

OBJECTIVE: To investigate the hot spot mutation of SLC26A4 gene and its incidence among patients with moderate to profound sensorineural hearing loss (SNHL) and to analyze the epidemiology of enlarged vestibular aqueduct syndrome in China. METHODS: Peripheral blood samples were collected from 1,552 students of deaf and dumb school in 21 cities throughout China. The nationality distribution of the 1,552 students included Han (n = 1290), Uigur (n = 69), Hui (n = 37), Mongolian (n = 31), and Southwest minorities including Yi, Zhuang, Bai, Miao and other 14 nationalities (n = 125). The hot spot mutation IVS7-2A > G and other mutations in the SLC26A4 exons 7 and 8 with intron 7 were analyzed by direct sequencing. RESULTS: Mutation in the SLC26A4 exons 7 and 8 or intron 7 were found in 199 students, of whom 83 carried IVS7-2A > G homozygous mutation, 114 carried IVS7-2A > G heterozygous mutation, and the other two carried two other kinds of mutation. Of the 1,552 cases, the percentage of cases carrying IVS7-2A > G mutation was 12.7% (197/1,552), and this percentage reached up to 14.3% in 1,290 cases of Han nationality, while in the 69 cases of Uigur nationality this ratio was 0. The prevalence rates of IVS7-2A > G mutation in Zhuozhou and Gaobeidian, Hebei province, and Anyang, Henan province, were 24.7% and 28.3% respectively, both significantly higher than the percentages of the whole China and other regions (all P < 0.05). CONCLUSION: Hereditary SNHL caused by SLC26A4 mutations accounts for a high percentage in China. It is of great importance to screen SLC26A4 gene for making etiological diagnosis for deafness. Screening of the hot spot mutation of IVS7-2A > G is of advantage for large scale screening among patients with deafness.