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

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 p...

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Bibliographic Details
Published in:Human genetics 2016-08, Vol.135 (8), p.953-961
Main Authors: 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
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Deafness
Deafness - epidemiology
Deafness - genetics
DNA
Ethnicity - genetics
Female
Gene Function
Genes
Genetic Testing
Genetics
Genetics, Population
Genomics
Hearing loss
Human Genetics
Humans
Iranian foreign relations
Male
Medical schools
Medicine
Metabolic Diseases
Molecular Medicine
Mutation
Neurosciences
Original Investigation
Otolaryngology
Usher Syndromes - epidemiology
Usher Syndromes - genetics
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Summary: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.
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-016-1697-z