Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents.
Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents.
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DOI：
10.1007/s00439-016-1697-z
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发表时间：
2016-08
期刊：
影响因子：
5.3
通讯作者：
Tekin M
中科院分区：
文献类型：
--
作者：
Yan D;Tekin D;Bademci G;Foster J 2nd;Cengiz FB;Kannan-Sundhari A;Guo S;Mittal R;Zou B;Grati M;Kabahuma RI;Kameswaran M;Lasisi TJ;Adedeji WA;Lasisi AO;Menendez I;Herrera M;Carranza C;Maroofian R;Crosby AH;Bensaid M;Masmoudi S;Behnam M;Mojarrad M;Feng Y;Duman D;Mawla AM;Nord AS;Blanton SH;Liu XZ;Tekin M
听力损失（HL）是人类最常见的感觉缺陷，在140多个基因中存在致病变异。然而，除了少数例外，许多已鉴定的变体/基因的群体特异性分布尚不清楚。直到最近，耳聋广泛的遗传和临床异质性排除了全面的遗传分析。在这里，使用自定义捕获面板（MiamiOtoGenes），我们对来自南非，尼日利亚，突尼斯，土耳其，伊朗，印度，危地马拉和美国（南佛罗里达）的342名GJB 2突变阴性耳聋先证者的多种族队列中的180个基因进行了靶向测序。我们在25%的多重和7%的单纯性家庭中检测到致病性DNA变异。根据种族的不同，检测率在0%到57%之间，危地马拉和伊朗分别处于较低和较高的水平。我们在27个基因中检测到致病变异，而没有主要的复发致病变异。最常涉及的基因包括MYO 15 A、SLC 26 A4、USH 2A、MYO 7A、MYO 6和TRIOBP。总的来说，我们的研究强调了家族史和多种族离散人群数据库生成的重要性，以提高我们检测和准确解释致病性遗传变异的能力。
Hearing loss (HL) is the most common sensory deficit in humans with causative variants in over 140 genes. With few exceptions, however, the population-specific distribution for many of the identified variants/genes is unclear. Until recently, the extensive genetic and clinical heterogeneity of deafness precluded comprehensive genetic analysis. Here, using a custom capture panel (MiamiOtoGenes), we undertook a targeted sequencing of 180 genes in a multi-ethnic cohort of 342 GJB2 mutation-negative deaf probands from South Africa, Nigeria, Tunisia, Turkey, Iran, India, Guatemala and the United States (South Florida). We detected causative DNA variants in 25% of multiplex and 7% of simplex families. The detection rate varied between 0% and 57% based on ethnicity, with Guatemala and Iran at the lower and higher end of the spectrum, respectively. We detected causative variants within 27 genes without predominant recurring pathogenic variants. The most commonly implicated genes include MYO15A, SLC26A4, USH2A, MYO7A, MYO6 and TRIOBP. Overall, our study highlights the importance of family history and generation of databases for multiple ethnically discrete populations to improve our ability to detect and accurately interpret genetic variants for pathogenicity.