Molecular epidemiology and functional assessment of novel allelic variants of SLC26A4 in non-syndromic hearing loss patients with enlarged vestibular aqueduct in China.
Molecular epidemiology and functional assessment of novel allelic variants of SLC26A4 in non-syndromic hearing loss patients with enlarged vestibular aqueduct in China.
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中国前庭导水管扩大非综合征性听力损失患者中 SLC26A4 新型等位基因变异的分子流行病学和功能评估
DOI：
10.1371/journal.pone.0049984
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dai P
中科院分区：
文献类型：
--
作者：
Yuan Y;Guo W;Tang J;Zhang G;Wang G;Han M;Zhang X;Yang S;He DZ;Dai P
编码pendrin的SLC26A4突变是耳聋的常见原因。SLC 26 A4突变导致Pendred综合征和非综合征性前庭水管扩大（伊娃）。SLC26A4的突变谱在不同种族群体中差异很大。为了解伊娃在中国人群中的发病情况，并为携带SLC26 A4变异的患者提供合适的基因检测和咨询，我们开展了一项大规模的SLC26 A4分子流行病学调查。方法收集2352例来自中国27个不同地区的非综合征性听力损失患者。对SLC26A4基因的热点区域外显子8、10和19进行测序。对于在热点区域具有一个等位基因变异的患者，对其他外显子逐一测序，直到鉴定出两个突变等位基因。然后通过颞骨计算机断层扫描检查SLC26 A4变异患者，以进行伊娃的放射学诊断。克隆了10个SLC26A4变体用于功能研究。共聚焦显微镜和放射性同位素技术用于检查pendrin的膜表达和转运功能。结果发现86种变异类型，其中47种从未报道过。中国聋人伊娃的比例至少为11%，汉族聋人至少为13%。SLC26A4基因的突变谱和突变检出率在中国大陆不同种族和地区之间存在差异。大多数变体引起pendrin在细胞内区域的保留。所有的突变pendrins表现出显着降低的运输能力。结论对我国SLC26A4的分子流行病学研究结果进行了全面描述。功能评估程序可用于鉴定变异体的致病性。这些结果对伊娃家系的遗传学诊断、遗传咨询、产前检测和着床前诊断具有重要的参考价值。
Background Mutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations are responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA). The mutation spectrum of SLC26A4 varies widely among ethnic groups. To investigate the incidence of EVA in Chinese population and to provide appropriate genetic testing and counseling to patients with SLC26A4 variants, we conducted a large-scale molecular epidemiological survey of SLC26A4. Methods A total of 2352 unrelated non-syndromic hearing loss patients from 27 different regions of China were included. Hot spot regions of SLC26A4, exons 8, 10 and 19 were sequenced. For patients with one allelic variant in the hot spot regions, the other exons were sequenced one by one until two mutant alleles had been identified. Patients with SLC26A4 variants were then examined by temporal bone computed tomography scan for radiological diagnosis of EVA. Ten SLC26A4 variants were cloned for functional study. Confocal microscopy and radioisotope techniques were used to examine the membrane expression of pendrin and transporter function. Results Of the 86 types of variants found, 47 have never been reported. The ratio of EVA in the Chinese deaf population was at least 11%, and that in patients of Han ethnicity reached at least 13%. The mutational spectrum and mutation detection rate of SLC26A4 are distinct among both ethnicities and regions of Mainland China. Most of the variants caused retention of pendrin in the intracellular region. All the mutant pendrins showed significantly reduced transport capability. Conclusion An overall description of the molecular epidemiological findings of SLC26A4 in China is provided. The functional assessment procedure can be applied to identification of pathogenicity of variants. These findings are valuable for genetic diagnosis, genetic counseling, prenatal testing and pre-implantation diagnosis in EVA families.
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内蒙古听力障碍的分子病因学：SLC26A4基因突变及相关表型分析。
影响因子：
7.4
作者：
Dai, Pu;Yuan, Yongyi;Wong, Lee-Jun C.
通讯作者：
Wong, Lee-Jun C.
影响因子：
3.5
作者：
Park, HJ;Lee, SJ;Koo, SK
通讯作者：
Koo, SK
影响因子：
4
作者：
Pryor, SP;Madeo, AC;Griffith, AJ
通讯作者：
Griffith, AJ
DOI：
10.1152/ajprenal.00037.2002
发表时间：
2002-10-01
影响因子：
4.2
作者：
Kim, YH;Kwon, TH;Nielsen, S
通讯作者：
Nielsen, S
影响因子：
3.9
作者：
Choi, Byung Yoon;Stewart, Andrew K.;Madeo, Anne C.;Pryor, Shannon P.;Lenhard, Suzanne;Kittles, Rick;Eisenman, David;Kim, H. Jeffrey;Niparko, John;Thomsen, James;Arnos, Kathleen S.;Nance, Walter E.;King, Kelly A.;Zalewski, Christopher K.;Brewer, Carmen C.;Shawker, Thomas;Reynolds, James C.;Butman, John A.;Karniski, Lawrence P.;Alper, Seth L.;Griffith, Andrew J.
通讯作者：
Griffith, Andrew J.