Yan Denise, Tekin Demet, Bademci Guney, Foster Joseph, Cengiz F Basak, Kannan-Sundhari Abhiraami, Guo Shengru, Mittal Rahul, Zou Bing, Grati Mhamed, Kabahuma Rosemary I, Kameswaran Mohan, Lasisi Taye J, Adedeji Waheed A, Lasisi Akeem O, Menendez Ibis, Herrera Marianna, Carranza Claudia, Maroofian Reza, Crosby Andrew H, Bensaid Mariem, Masmoudi Saber, Behnam Mahdiyeh, Mojarrad Majid, Feng Yong, Duman Duygu, Mawla Alex M, Nord Alex S, Blanton Susan H, Liu Xue Z, Tekin Mustafa
Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA.
Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.
Hum Genet. 2016 Aug;135(8):953-61. doi: 10.1007/s00439-016-1697-z. Epub 2016 Jun 25.
Hearing loss 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.
听力损失是人类中最常见的感觉缺陷，有超过140个基因存在致病变体。然而，除了少数例外情况，许多已鉴定变体/基因的人群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阻碍了全面的遗传分析。在此，我们使用定制捕获面板（迈阿密耳基因），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GJB2突变阴性耳聋先证者的多民族队列中的180个基因进行了靶向测序。我们在25%的多重家庭和7%的单重家庭中检测到致病DNA变体。根据种族不同，检测率在0%至57%之间变化，危地马拉和伊朗分别处于该范围的低端和高端。我们在27个基因中检测到致病变体，没有主要的反复出现的致病变体。最常涉及的基因包括MYO15A、SLC26A4、USH2A、MYO7A、MYO6和TRIOBP。总体而言，我们的研究强调了家族史以及为多个种族离散人群建立数据库的重要性，以提高我们检测和准确解释致病基因变体的能力。
