Study of the Association of DFNB3 Locus with Autosomal Recessive Non-Syndromic Hearing Loss in Iranian Deaf Population Using Genetic Linkage Analysis

Document Type : Original Article (s)

Authors

1 PhD Student, Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

2 Associate Professor, Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

3 Assistant Professor, Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Professor, Department of Medical Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

5 Assistant Professor, Department of Molecular Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

6 Cellular and Molecular Research Center, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran

7 Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

8 Professor, Cellular and Molecular Research Center, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran

Abstract

Background: Hearing loss is a common sensory disorder that typically illustrates genetic heterogeneity in human populations. The incidence of congenital hearing loss is estimated at 1 in 500 births of which approximately 70% of cases are attributed to genetic factors. Genetic hearing impairment can be classified as either syndromic or non-syndromic and among non-syndromic hearing loss autosomal recessive (ALNSHL) accounts for approximately 75-80% of cases. This type of hearing loss is extremely heterogeneous and includes over 100 loci. For recessive deafness, most frequent genes are GJB2, SLC26A4, MYO15A, OTOF, and CDH23 in worldwide. This study aimed to determine the role of MYO15A (DFNB3) gene mutations in Iranian deaf population using linkage analysis.Methods: To investigate the frequency of DFNB3 gene mutation, linkage analysis was performed in 30 Iranian families with over three deaf child and negative GJB2. The negative mutations pedigrees for these gene mutations were then tested for the linkage to DFNB3 (MYO15A) locus, using short tandem repeat (STR) markers.Findings: Mutation 35delG was identified in 5 families out of 30 by sequencing the coding region of GJB2 gene. One family showed linkage to DFNB3 locus.Conclusion: Based on the results of this study, DFNB3 locus is the third cause of deafness after DFNB1 (GJB2) and DFNB4 (SLC26A4).

Keywords

References

  1. Morton CC, Nance WE. Newborn hearing screening--a silent revolution. N Engl J Med 2006; 354(20): 2151-64.
  2. Collin RW, Kalay E, Oostrik J, Caylan R, Wollnik B, Arslan S, et al. Involvement of DFNB59 mutations in autosomal recessive nonsyndromic hearing impairment. Hum Mutat 2007; 28(7): 718-23.
  3. Van CG, Willems PJ, Smith RJ. Nonsyndromic hearing impairment: unparalleled heterogeneity. Am J Hum Genet 1997; 60(4): 758-64.
  4. Hilgert N, Smith RJ, Van CG. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat Res 2009; 681(2-3): 189-96.
  5. Kenneson A, Van Naarden BK, Boyle C. GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review. Genet Med 2002; 4(4): 258-74.
  6. Strachan T, Read A. human molecular genetics. New York, NY: Garland Science; 2011.
  7. Hashemzadeh Chaleshtori M, Farhud D, Patton M. Congratulation to Margaret Chan familial and sporadic Gjb2-related deafness in Iran: review of gene mutations. Iran J Public Health 2007; 36(1): 1-14.
  8. Mahdieh N, Rabbani B, Shirkavand A, Bagherian H, Movahed ZS, Fouladi P, et al. Impact of consanguineous marriages in GJB2-related hearing loss in the Iranian population: a report of a novel variant. Genet Test Mol Biomarkers 2011; 15(7-8): 489-93.
  9. Najmabadi H, Nishimura C, Kahrizi K, Riazalhosseini Y, Malekpour M, Daneshi A, et al. GJB2 mutations: passage through Iran. Am J Med Genet A 2005; 133A(2): 132-7.
  10. Sininger Y, Starr A. Auditory neuropathy: a new perspective on hearing disorders. Stamford, CT: Cengage Learning; 2001.
  11. Smith RJH, Shearer AE, Hildebrand MS, van Camp G. Deafness and hereditary hearing loss overview. Gene review sat Gene Tests: Medical genetics information resource. Seattle, WA: University of Washington; 1999. 2008.
  12. Anderson DW, Probst FJ, Belyantseva IA, Fridell RA, Beyer L, Martin DM, et al. The motor and tail regions of myosin XV are critical for normal structure and function of auditory and vestibular hair cells. Hum Mol Genet 2000; 9(12): 1729-38.
  13. Belyantseva IA, Boger ET, Friedman TB. Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle. Proc Natl Acad Sci U S A 2003; 100(24): 13958-63.
  14. Liang Y, Wang A, Belyantseva IA, Anderson DW, Probst FJ, Barber TD, et al. Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2. Genomics 1999; 61(3): 243-58.
  15. Grimberg J, Nawoschik S, Belluscio L, McKee R, Turck A, Eisenberg A. A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Res 1989; 17(20): 8390.
  16. Kleihues P, Schauble B, zur HA, Esteve J, Ohgaki H. Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol 1997; 150(1): 1-13.
  17. Lindner TH, Hoffmann K. easyLINKAGE: a PERL script for easy and automated two-/multi-point linkage analyses. Bioinformatics 2005; 21(3): 405-7.
  18. Thiele H, Nurnberg P. HaploPainter: a tool for drawing pedigrees with complex haplotypes. Bioinformatics 2005; 21(8): 1730-2.
  19. Liburd N, Ghosh M, Riazuddin S, Naz S, Khan S, Ahmed Z, et al. Novel mutations of MYO15A associated with profound deafness in consanguineous families and moderately severe hearing loss in a patient with Smith-Magenis syndrome. Hum Genet 2001; 109(5): 535-41.
  20. Berg JS, Powell BC, Cheney RE. A millennial myosin census. Mol Biol Cell 2001; 12(4): 780-94.
  21. Cengiz FB, Duman D, Sirmaci A, Tokgoz-Yilmaz S, Erbek S, Ozturkmen-Akay H, et al. Recurrent and private MYO15A mutations are associated with deafness in the Turkish population. Genet Test Mol Biomarkers 2010; 14(4): 543-50.
  22. Fattahi Z, Shearer AE, Babanejad M, Bazazzadegan N, Almadani SN, Nikzat N, et al. Screening for MYO15A gene mutations in autosomal recessive nonsyndromic, GJB2 negative Iranian deaf population. Am J Med Genet A 2012; 158A(8): 1857-64.
  23. Sadeghi A, Sanati MH, Alasti F, Hashemzadeh Chaleshtori M, Mahmoudian S, Ataei M. Contribution of GJB2 Mutations and Four Common DFNB Loci in Autosomal Recessive Non-Syndromic Hearing Impairment in Markazi and Qom Provinces of Iran. Iran J Biotech 2009; 7(2): 108-11.
Journal of Isfahan Medical School
Volume 32, Issue 285 - Serial Number 285
March and April 2014
Pages 669-677

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History

  • Receive Date: 30 March 2014
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

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