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

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• 作者：Denise Yan ; Demet Tekin ; Guney Bademci ; Joseph Foster II ; F. Basak Cengiz…
• 刊名：Human Genetics
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：135
• 期：8
• 页码：953-961
• 全文大小：549 KB
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• 作者单位：Denise Yan (1)
  Demet Tekin (1)
  Guney Bademci (2)
  Joseph Foster II (1) (2)
  F. Basak Cengiz (2)
  Abhiraami Kannan-Sundhari (1)
  Shengru Guo (2)
  Rahul Mittal (1)
  Bing Zou (1)
  Mhamed Grati (1)
  Rosemary I. Kabahuma (3)
  Mohan Kameswaran (4)
  Taye J. Lasisi (5)
  Waheed A. Adedeji (5)
  Akeem O. Lasisi (5)
  Ibis Menendez (2)
  Marianna Herrera (6)
  Claudia Carranza (6)
  Reza Maroofian (7)
  Andrew H. Crosby (7)
  Mariem Bensaid (8)
  Saber Masmoudi (8)
  Mahdiyeh Behnam (9)
  Majid Mojarrad (10)
  Yong Feng (11)
  Duygu Duman (12)
  Alex M. Mawla (13) (14)
  Alex S. Nord (13) (14)
  Susan H. Blanton (1) (15) (2)
  Xue Z. Liu (1) (11) (2)
  Mustafa Tekin (1) (15) (2)
  
  1. Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL, 33136, USA
  2. 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
  3. Department of Otorhinolaryngology, Steve Biko Academic Hospital, University of Pretoria, Cnr Malan and Steve Biko Road, Gezina, Pretoria, South Africa
  4. Madras ENT Research Foundation (MERF), No-1, 1st Cross Street, Off. II Main Road, Raja Annamalai Puram, Chennai, 600028, Tamil Nadu, India
  5. Department of Otorhinolaryngology, College of Medicine, University of Ibadan, Ibadan, Nigeria
  6. Institute for Research on Genetic and Metabolic Diseases, INVEGEM, Guatemala City, Guatemala
  7. Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD Wellcome Wolfson Centre, Exeter, UK
  8. Laboratoire Procédés de Criblage Moléculaire et Cellulaire, Centre de Biotechnologie de Sfax, Université de Sfax, Sfax, Tunisia
  9. Medical Genetics Laboratory of Genome, Isfahan, Iran
  10. Department of Medical Genetics, Mashhad University of Medical Sciences, Mashhad, Iran
  11. Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China
  12. Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey
  13. Department of Neurobiology, Physiology, and Behavior, Center for Neuroscience, UC Davis, Davis, CA, 95616, USA
  14. Department of Psychiatry and Behavioral Sciences, Center for Neuroscience, UC Davis, Davis, CA, 95616, USA
  15. Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Human Genetics
  Molecular Medicine
  Internal Medicine
  Metabolic Diseases
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1203
• 卷排序：135

文摘

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. Electronic supplementary materialThe online version of this article (doi:10.​1007/​s00439-016-1697-z) contains supplementary material, which is available to authorized users.