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Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran
  1. Christina M Sloan-Heggen1,2,
  2. Mojgan Babanejad3,
  3. Maryam Beheshtian3,
  4. Allen C Simpson1,
  5. Kevin T Booth1,
  6. Fariba Ardalani3,
  7. Kathy L Frees1,
  8. Marzieh Mohseni3,
  9. Reza Mozafari3,
  10. Zohreh Mehrjoo3,
  11. Leila Jamali3,
  12. Saeideh Vaziri3,
  13. Tara Akhtarkhavari3,
  14. Niloofar Bazazzadegan3,
  15. Nooshin Nikzat3,
  16. Sanaz Arzhangi3,
  17. Farahnaz Sabbagh4,
  18. Hasan Otukesh5,
  19. Seyed Morteza Seifati6,
  20. Hossein Khodaei6,
  21. Maryam Taghdiri7,
  22. Nicole C Meyer1,
  23. Ahmad Daneshi8,
  24. Mohammad Farhadi8,
  25. Kimia Kahrizi3,
  26. Richard JH Smith1,2,9,
  27. Hela Azaiez1,
  28. Hossein Najmabadi3
  1. 1Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
  2. 2Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
  3. 3Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
  4. 4Genetics Counseling Center, Kerman Welfare Institution, Kerman, Iran
  5. 5Division of Pediatric Nephrology, Hazrat-e-Ali Asghar Educational & Treatment Center, Iran University of Medical Sciences, Tehran, Iran
  6. 6Meybod Genetics Research Center, Shahid Fiazbakhsh Rehabilitation Comprehensive Center, Welfare Organization, Yazd, Iran
  7. 7Genetic Counseling Center, Shiraz Welfare Institution, Shiraz, Iran
  8. 8Head and Neck Surgery Department and Research Center, Iran University of Medical Sciences, Tehran, Iran
  9. 9Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, Iowa, USA
  1. Correspondence to Professor Hossein Najmabadi, Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; hnajm12@yahoo.com Hela Azaiez, Molecular Otolarygology and Renal Reseach Laboratories, 200 Hawkins Drive, Iowa City, IA 52242, USA; hela-azaiez@uiowa.eduProfessor Richard JH Smith, Molecular Otolaryngology and Renal Research Laboratories, 200 Hawkins Drive, Iowa City, IA 52242, USA; richard-smith{at}uiowa.edu

Abstract

Background Countries with culturally accepted consanguinity provide a unique resource for the study of rare recessively inherited genetic diseases. Although hereditary hearing loss (HHL) is not uncommon, it is genetically heterogeneous, with over 85 genes causally implicated in non-syndromic hearing loss (NSHL). This heterogeneity makes many gene-specific types of NSHL exceedingly rare. We sought to define the spectrum of autosomal recessive HHL in Iran by investigating both common and rarely diagnosed deafness-causing genes.

Design Using a custom targeted genomic enrichment (TGE) panel, we simultaneously interrogated all known genetic causes of NSHL in a cohort of 302 GJB2-negative Iranian families.

Results We established a genetic diagnosis for 67% of probands and their families, with over half of all diagnoses attributable to variants in five genes: SLC26A4, MYO15A, MYO7A, CDH23 and PCDH15. As a reflection of the power of consanguinity mapping, 26 genes were identified as causative for NSHL in the Iranian population for the first time. In total, 179 deafness-causing variants were identified in 40 genes in 201 probands, including 110 novel single nucleotide or small insertion–deletion variants and three novel CNV. Several variants represent founder mutations.

Conclusion This study attests to the power of TGE and massively parallel sequencing as a diagnostic tool for the evaluation of hearing loss in Iran, and expands on our understanding of the genetics of HHL in this country. Families negative for variants in the genes represented on this panel represent an excellent cohort for novel gene discovery.

  • Neurosciences
  • Molecular genetics
  • Diagnostics tests
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