Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents

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

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)953-961
Number of pages9
JournalHuman genetics
Volume135
Issue number8
DOIs
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Yan, D., Tekin, D., Bademci, G., Foster, J., Cengiz, F. B., Kannan-Sundhari, A., Guo, S., Mittal, R., Zou, B., Grati, MH., Kabahuma, R. I., Kameswaran, M., Lasisi, T. J., Adedeji, W. A., Lasisi, A. O., Menendez, I., Herrera, M., Carranza, C., Maroofian, R., ... Tekin, M. (2016). Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents. Human genetics, 135(8), 953-961. https://doi.org/10.1007/s00439-016-1697-z