Journal Article

Spectrum of DNA variants for nonsyndromic deafness in a large cohort from multiple continents

Kameswaran, Mohan, Bensaid, Mariem, Mojarrad, Majid, Feng, Yong, Tekin, Demet, Tekin, Mustafa, Masmoudi, Saber, Maroofian, Reza, Mawla, Alex M., Bademci, Guney, Carranza, Claudia, Behnam, Mahdiyeh, Adedeji, Waheed A, Grati, Mhamed, Nord, Alex S., Cengiz, F. Basak, Blanton, Susan H., Kabahuma, Rosemary I., Liu, Xuezhong, Lasisi, Akeem O., Mittal, Rahul, Yan, Denise, Kannan-Sundhari, Abhiraami, Foster, Joseph, Lasisi, Taye J, Crosby, Andrew H., Herrera, Marianna, Duman, Duygu, Zou, Bing, Menendez, Ibis, Guo, Shengru

2016

Overview

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.