Genetic Linkage Analysis of the DFNB63 Locus in Families with Autosomal Recessive Nonsyndromic Hearing Loss from Hamadan and Kohgiluyeh and Boyer-Ahmad Provinces, Iran

Document Type : Original Article (s)

Authors

1 Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

2 Assistant Professor, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Assistant Professor, Department of Genetics, School of Science, Shahrekord University, Shahrekord, Iran

4 Professor, Cellular and Molecular Research Center AND Department of Medical Genetics, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran

Abstract

Background: Hearing loss is a sensorineural impairment and is one of the most widespread congenital impairments with a prevalence of one in thousand among children. Studies have shown that 50 percent of congenital hearing loss have genetic causes and the remaining 50 percent are due to environment and unknown reasons; in addition, it is noted that this impairment is very heterogeneous. Almost 70 percent of cases are nonsyndromic with hearing loss presenting as the only impairment. About 80 percent of this type of hearing loss is inherited in recessive manner (ARNSHL). In this study, we determined the role of DFNB63 locus in a series of families in two western provinces of Iran.Methods: In this descriptive-laboratory study, to determine the prevalence of DFNB63 mutations in western provinces of Iran, we studied 150 individuals from 30 families in Hamadan and Kohgiluyeh and Boyer-Ahmad provinces. The selected families in this study were consanguineous, had at least 2 patients, and were negative for GJB2 mutations. Linkage analysis was performed using six appropriate short tandem repeats (STR) markers.Findings: With linkage analysis of selected families, no family was shown to be linked to the DFNB63 locus. It was shown that the LRTOMT mutations played no role in causing hearing loss in the studied families.Conclusion: The present study suggests that LRTOMT mutations may not be clinically important in causing autosomal recessive nonsyndromic hearing loss in the investigated provinces. 

Keywords

References

  1. Bitner-Glindzicz M. Hereditary deafness and phenotyping in humans. Br Med Bull 2002; 63: 73-94.
  2. Tekin M, Arnos KS, Pandya A. Advances in hereditary deafness. Lancet 2001; 358(9287): 1082-90.
  3. Van Laer L, Cryns K, Smith RJ, Van Camp G. Nonsyndromic hearing loss. Ear Hear 2003; 24(4): 275-88.
  4. Genc GA, Konukseven O, Muluk NB, Kirkim G, Basar FS, Tuncer U, et al. Features of unilateral hearing loss detected by newborn hearing screening programme in different regions of Turkey. Auris Nasus Larynx 2013; 40(3): 251-9.
  5. Morton NE. Genetic epidemiology of hearing impairment. Ann N Y Acad Sci 1991; 630: 16-31.
  6. Dror AA, Avraham KB. Hearing loss: mechanisms revealed by genetics and cell biology. Annu Rev Genet 2009; 43: 411-37.
  7. 7. Van Camp G, Smith RJ. Hereditary hearing loss homepage [Online]. [cited 2015 May 13]; Available from: URL: http://hereditaryhearingloss.org/
  8. Tabatabaiefar M, Alasti F, Zohour MM, Shariati L, Farrokhi E, Farhud D, et al. Genetic Linkage Analysis of 15 DFNB Loci in a Group of Iranian Families with Autosomal Recessive Hearing Loss. Iran J Public Health 2011; 40(2): 34-48.
  9. Hashemzadeh Chaleshtori M, Farhud DD, Patton MA. 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.
  10. 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.
  11. Ahmed ZM, Masmoudi S, Kalay E, Belyantseva IA, Mosrati MA, Collin RW, et al. Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans. Nat Genet 2008; 40(11): 1335-40.
  12. Kalay E, Caylan R, Kiroglu AF, Yasar T, Collin RW, Heister JG, et al. A novel locus for autosomal recessive nonsyndromic hearing impairment, DFNB63, maps to chromosome 11q13.2-q13.4. J Mol Med (Berl ) 2007; 85(4): 397-404.
  13. Moser T, Predoehl F, Starr A. Review of hair cell synapse defects in sensorineural hearing impairment. Otol Neurotol 2013; 34(6): 995-1004.
  14. Ott J. Computer-simulation methods in human linkage analysis. Proc Natl Acad Sci USA 2015; 86(11): 4175-8.
  15. Tabatabaiefar MA, Alasti F, Shariati L, Farrokhi E, Fransen E, Nooridaloii MR, et al. DFNB93, a novel locus for autosomal recessive moderate-to-severe hearing impairment. Clin Genet 2011; 79(6): 594-8.
  16. Vanwesemael M, Schrauwen I, Ceuppens R, Alasti F, Jorssen E, Farrokhi E, et al. A 1 bp deletion in the dual reading frame deafness gene LRTOMT causes a frameshift from the first into the second reading frame. Am J Med Genet A
  17. ; 155A(8): 2021-3.
  18. Taghizadeh SH, Kazeminezhad SR, Sefidgar SA, Yazdanpanahi N, Tabatabaeifar MA, Yousefi A, et al. Investigation of LRTOMT gene (locus DFNB63) mutations in Iranian patients with autosomal recessive non-syndromic hearing loss. Int J Mol Cell Med 2013; 2(1): 41-5.
  19. Du X, Schwander M, Moresco EM, Viviani P, Haller C, Hildebrand MS, et al. A catechol-O-methyltransferase that is essential for auditory function in mice and humans. Proc Natl Acad Sci USA 2008; 105(38): 14609-14.
  20. Tabatabaiefar MA, Shariati L, Montazer-Zohour M, Ashrafi K, Saffari-Chaleshtori J, Ghasemikhah R, et al. Mutation screening of GJB2 and GJB6 and genetic linkage study of three prevalent DFNB loci in Iranian families with Autosomal recessive non-Syndromic hearing loss. J Shahrekord Univ Med Sci 2010; 12(2): 65-75. [In Persian].
  21. Schrauwen I, Helfmann S, Inagaki A, Predoehl F, Tabatabaiefar MA, Picher MM, et al. A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment. Am J Hum Genet 2012; 91(4): 636-45.
Journal of Isfahan Medical School
Volume 33, Issue 346 - Serial Number 346
July and August 2015
Pages 1308-1317

Files

History

  • Receive Date: 29 May 2015
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics