Novel compound heterozygous TMC1 mutations associated with autosomal recessive hearing loss in a Chinese family.
Novel compound heterozygous TMC1 mutations associated with autosomal recessive hearing loss in a Chinese family.
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与中国家庭常染色体隐性听力损失相关的新型复合杂合 TMC1 突变
DOI：
10.1371/journal.pone.0063026
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发表时间：
2013
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：
Gao X;Su Y;Guan LP;Yuan YY;Huang SS;Lu Y;Wang GJ;Han MY;Yu F;Song YS;Zhu QY;Wu J;Dai P
遗传性非综合征性听力损失是高度异质性的，大多数假定遗传病因的患者缺乏特异性诊断。据估计，数百个基因可能与人类的这种感觉缺陷有关。在此，我们通过对一个有两个耳聋兄弟姐妹的家庭进行全外显子组测序，确定了TMC1基因的复合杂合突变是复发性遗传性感音神经性听力损失的原因。桑格测序证实，这两个兄弟姐妹都遗传了TMC 1中的错义突变c.589 G>A p.G197 R（母系等位基因）和无义突变c.1171 C>T p.Q391 X（父系等位基因）。我们还使用了50例中国家族性ARNSHL患者和208例种族匹配的阴性样本的DNA进行扩展变异分析。这两种变异在具有听力损失表型的家族1953中共分离，但在50名患者和208名种族匹配的对照中不存在。因此，我们得出结论，该家族的听力损失是由TMC 1的新型复合杂合突变引起的。
Hereditary nonsyndromic hearing loss is highly heterogeneous and most patients with a presumed genetic etiology lack a specific diagnosis. It has been estimated that several hundred genes may be associated with this sensory deficit in humans. Here, we identified compound heterozygous mutations in the TMC1 gene as the cause of recessively inherited sensorineural hearing loss by using whole-exome sequencing in a family with two deaf siblings. Sanger sequencing confirmed that both siblings inherited a missense mutation, c.589G>A p.G197R (maternal allele), and a nonsense mutation, c.1171C>T p.Q391X (paternal allele), in TMC1. We also used DNA from 50 Chinese familial patients with ARNSHL and 208 ethnicity-matched negative samples to perform extended variants analysis. Both variants co-segregated in family 1953, which had the hearing loss phenotype, but were absent in 50 patients and 208 ethnicity-matched controls. Therefore, we concluded that the hearing loss in this family was caused by novel compound heterozygous mutations in TMC1.
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影响因子：
12.3
作者：
Brownstein Z;Bhonker Y;Avraham KB
通讯作者：
Avraham KB
TMC1的突变分析鉴定了四个新突变，并提出了位点DFNA36和DFNB7/11的额外耳聋基因。
影响因子：
3.5
作者：
Hilgert N;Alasti F;Dieltjens N;Pawlik B;Wollnik B;Uyguner O;Delmaghani S;Weil D;Petit C;Danis E;Yang T;Pandelia E;Petersen MB;Goossens D;Favero JD;Sanati MH;Smith RJ;Van Camp G
通讯作者：
Van Camp G
影响因子：
2.8
作者：
Shearer, A. Eliot;Hildebrand, Michael S.;Sloan, Christina M.;Smith, Richard J. H.
通讯作者：
Smith, Richard J. H.
影响因子：
3.9
作者：
Santos, Regie Lyn P;Wajid, Muhammad;Leal, Suzanne M
通讯作者：
Leal, Suzanne M
影响因子：
30.8
作者：
Kurima, K;Peters, LM;Griffith, AJ
通讯作者：
Griffith, AJ