SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause of hearing loss
SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause of hearing loss
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DOI：
10.1097/gim.0b013e31817d2ef1
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发表时间：
2008-08-01
影响因子：
8.8
通讯作者：
Wu, Bai-Lin
中科院分区：
文献类型：
--
作者：
Dai, Pu;Li, Qi;Wu, Bai-Lin
目的：SLC 26 A4基因突变是仅次于GJB 2突变的感音神经性耳聋的第二大遗传原因。在中国大部分地区，由于对突变谱的了解有限，无法进行感音神经性听力损失的基因检测。虽然SLC 26 A4 c.919-2A>G（IVS 7 -2A>G）是亚洲人群中常见的突变，但在中国各民族中的突变流行率尚未研究。研究方法：应用聚合酶链反应/限制性片段长度多态性技术对来自中国27个地区的3271例中重度感音神经性耳聋患者的DNA标本进行c.919-2A>G突变的基因分型。汉族（n = 185）和维吾尔族（n = 152）听力正常者也进行了测试。结果如下：总体而言，408名感音神经性听力损失受试者（12.5%）携带至少一个c.919-2A>G等位基因，其中158名（4.8%）为纯合子，250名（7.6%）为杂合子。在所检测的亚群中，c.919-2A>G纯合子的比率为0%至12.2%，杂合子的比率为0%至17.6%。基于该队列，中国感音神经性听力损失受试者似乎比其他亚洲人群具有相对较高的c.919-2A>G频率。结论：这些结果表明，仅对c.919-2A>G突变进行简单有效的基因检测，就可以在中国东部和中部的一些地区确定高达8-12%的感音神经性听力损失个体的分子病因。c.919-2A>G突变阴性者可作为进一步分析SLC 26 A4或其他生殖相关基因突变的候选者。这将极大地改善对中国大量感音神经性听力损失患者和家庭成员的遗传诊断和咨询，以及其他国家更多的中国人，可能高达100万。
Purpose: Mutations in the SLC26A4 gene are second only to GJB2 mutations as a currently identifiable genetic cause of sensorineural hearing loss. In most areas of China, genetic testing for sensorineural hearing loss is unavailable because of limited knowledge of the mutation spectrum. Although SLC26A4 c.919-2A>G (IVS7-2A>G) is a common mutation among some Asian populations, the mutation prevalence among various ethnic groups within China has not been studied. Methods: DNA specimens from 3271 subjects with moderate to profound sensorineural hearing loss from 27 regions of China were genotyped for the c.919-2A>G mutation by polymerase chain reaction/restriction-fragment-length polymorphism. Normal hearing controls from Han (n = 185) and Uigur (n = 152) populations were also tested. Results: Overall, 408 subjects with sensorineural hearing loss (12.5%) carried at least one c.919-2A>G allele, with 158 (4.8%) homozygotes and 250 (7.6%) heterozygotes. Within the subpopulations examined, the rate varies from 0% to 12.2% for c.919-2A>G homozygotes and from 0% to 17.6% for heterozygotes. Based on this cohort, Chinese subjects with sensorineural hearing loss seem to have a relatively higher c.919-2A>G frequency than that of other Asian populations. Conclusion: These results demonstrate that a simple and efficient genetic test for the c.919-2A>G mutation alone would identify the molecular cause in up to 8-12% of individuals with sensorineural hearing loss in a few eastern and central regions of China. Those who are negative for the c.919-2A>G mutation would be candidates for further mutational analysis of SLC26A4 or other deafness-related genes. This would greatly improve genetic diagnosis and counseling for a huge number of Chinese individuals and family members with sensorineural hearing loss in China, and many more ethnic Chinese in other countries, which might be up to one million.