Screening of 10 DFNB Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for GJB2 Mutations
-
Mahbobeh KOOHIYAN
,
Somayeh REIISI
,
Fatemeh AZADEGAN-DEHKORDI
,
Mansoor SALEHI
,
Hamidreza ABTAHI
,
Morteza HASHEMZADEH-CHALESHTORI
,
Mohammad Reza NOORI-DALOII
,
Mohammad Amin TABATABAIEFAR
Abstract
Background: Autosomal recessive non-syndromic hearing loss (ARNSHL), one of the global public health concerns, is marked by a high degree of genetic heterogeneity. The role of GJB2, as the most common cause of ARNSHL, is only <20% in the Iranian population. Here, we aimed to determine the relative contribution of several apparently most common loci in a cohort of ARNSHL Iranian families that were negative for the GJB2 mutations.
Methods: Totally, 80 Iranian ARNSHL families with 3 or more affected individuals from Isfahan and Hamedan provinces, Iran were enrolled in 2017. After excluding mutations in the GJB2 gene via Sanger sequencing, 60 negative samples (30 families from each province) were analyzed using homozygosity mapping for 10 ARNSHL loci.
Results: Fourteen families were found to be linked to five different known loci, including DFNB4 (5 families), DFNB2 (3 families), DFNB7/11 (1 family), DFNB9 (2 families) and DFNB3 (3 families).
Conclusion: Despite the high heterogeneity of ARNSHL, the genetic causes were determined in 23.5% of the studied families using homozygosity mapping. This data gives an overview of the ARNSHL etiology in the center and west of Iran, used to establish a diagnostic gene panel including most common loci for hearing loss diagnostics.
1. Norouzi V, Azizi H, Fattahi Z, Esteghamat F et al (2011). Did the GJB2 35delG mutation originate in Iran? Am J Med Genet Part A, 155:2453-2458.
2. Masoudi M, Ahangari N, Zonouzi AAP et al (2016). Genetic Linkage Analysis of DFNB3, DFNB9 and DFNB21 Loci in GJB2 Negative Families with Autosomal Recessive Non-syndromic Hearing Loss. Iran J Public Health, 45:680-7.
3. Sanaz Arzhangi B, Kevin Booth B, Ahmad Daneshi M et al (2016). Heterogeneity of Hereditary Hearing Loss in Iran: a Comprehensive Review. Arch Iran Med, 19:720-728.
4. Chaleshtori MH, Zohour MM, Rad LH et al (2006). Autosomal recessive and sporadic non syndromic hearing loss and the incidence of Cx26 mutations in a Province of Iran. Iran J Public Health, 35:88-91.
5. Azadegan-Dehkordi F, Bahrami T, Shir-zad M et al (2019). Mutations in GJB2 as Major Causes of Autosomal Reces-sive Non-Syndromic Hearing Loss: First Report of c. 299-300delAT Mu-tation in Kurdish Population of Iran. J Audiol Otol, 23(1):20-26.
6. Saadat M (2005). Epidemiology and mortality of hospitalized burn patients in Kohkiluye va Boyerahmad province (Iran): 2002–2004. Burns, 31:306-309.
7. koohiyan M, Ahmadi A, koohian F et al (2019). An update of spectrum and frequency of GJB2 mutations causing hearing loss in the south of Iran: a literature review. Int J Pediatr Otorhinolaryngol, 119:136-140.
8. Koohiyan M, Chaleshtori MH, Salehi M et al (2018). GJB2 mutations causing autosomal recessive non-syndromic hearing loss (ARNSHL) in two Iranian populations: Report of two novel vari-ants. Int J Pediatr Otorhinolaryngol, 107:121-126.
9. Ghasemnejad T, Khaniani MS, Zarei F et al (2017). An update of common autosomal recessive non-syndromic hearing loss genes in Iranian population. Int J Pediatr Otorhinolaryngol, 97: 113-126.
10. Yan D, Xiang G, Chai X, Qing J et al (2017). Screening of deafness-causing DNA variants that are common in patients of European ancestry using a microarray-based approach. PloS one, 12:e0169219.
11. Lindner TH, Hoffmann K (2005). easyLINKAGE: a PERL script for easy and automated two-/multi-point linkage analyses. Bioinformatics, 21:405-407.
12. Fishelson M, Geiger D (2004). Optimizing exact genetic linkage computations. J Comput Biol, 11:263-275.
13. Koohiyan M (2019). A systematic review of SLC26A4 mutations causing hearing loss in the Iranian population. Int J Pediatr Otorhinolaryngol, 125:1-5.
14. Wu C-C, Lu Y-C, Chen P-J et al (2010). Phenotypic analyses and mutation screening of the SLC26A4 and FOXI1 genes in 101 Taiwanese families with bilateral nonsyndromic enlarged vestibular aqueduct (DFNB4) or Pendred syndrome. Audiol Neurootol, 15:57-66.
15. Kahrizi K, Mohseni M, Nishimura C et al (2009). Identification of SLC26A4 gene mutations in Iranian families with hereditary hearing impairment. Eur J Pediatr, 168:651-3.
16. Yazdanpanahi N, Tabatabaiefar MA, Farrokhi E et al (2013). Compound heterozygosity for two novel SLC26A4 mutations in a large Iranian pedigree with Pendred syndrome. Clin Exp Otorhinolaryngol, 6:201-208.
17. Hilgert N, Kahrizi K, Dieltjens N et al (2009). A large deletion in GPR98 causes type IIC Usher syndrome in male and female members of an Iranian family. J Med Genet, 46:272-276.
18. Tabatabaiefar M, Alasti F, Shariati L, Farrokhi E (2011). DFNB93, a novel locus for autosomal recessive moderate‐to‐severe hearing impairment. Clin Genet, 79:594-598.
19. Babanejad M, Fattahi Z, Bazazzadegan N et al (2012). A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran. Am J Med Genet Part A, 158:2485-2492.
20. Sloan-Heggen CM, Babanejad M, Beheshtian M et al (2015). Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran. J Med Genet, 52:823-829.
21. Friedman TB, Liang Y, Weber JL et al (1995). A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17. Nat genet, 9:86-91.
22. Cengiz FB, Duman D, Sırmacı A et al (2010). Recurrent and private MYO15A mutations are associated with deafness in the Turkish population. Genet Test Mol Biomarkers, 14:543-550.
23. Zarepour N, Koohiyan M, Taghipour-Sheshdeh A et al (2019). Identification and Clinical Implications of a Novel MYO15A Variant in a Consanguineous Iranian Family by Targeted Exome Sequencing. Audiol Neurootol , 24(1) :25-31.
24. Bashir R, Fatima A, Naz S (2012). Prioritized sequencing of the second exon of MYO15A reveals a new mutation segregating in a Pakistani family with moderate to severe hearing loss. Eur J Med Genet, 55:99-102.
25. Sadeghi A, Sanati MH, Alasti F et al (2009). 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 of Biotechnol, 7:108-111.
26. Choi BY, Ahmed ZM, Riazuddin S et al (2009). Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan. Clin genet, 75:237-243.
27. Chiu Y-H, Wu C-C, Lu Y-C et al (2010). Mutations in the OTOF gene in Taiwanese patients with auditory neuropathy. Audiol Neurootol, 15:364-374.
28. Tabatabaiefar M, Alasti F, Zohour MM et al (2011). Genetic linkage analysis of 15 DFNB loci in a group of Iranian families with autosomal recessive hearing loss. Iran J Public Health, 40:34-48.
29. Khosrofar M, Pourreza MR, Asgharzadeh S et al (2017). Genetic Linkage Analysis of the DFNB21 Locus in Autosomal Recessive Hearing Loss in Large Families from Khuzestan Province. Arak Medical University Journal, 20:31-38.
30. Schrauwen I, Helfmann S, Inagaki A et al (2012). A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment. Am J Med Genet, 91:636-645.
31. Kawashima Y, Géléoc GS, Kurima K et al (2011). Mechanotransduction in mouse inner ear hair cells requires transmembrane channel–like genes. J Clin Invest, 121:4796-809.
32. Davoudi-Dehaghani E, Zeinali S, Mahdieh N et al (2013). A transversion mutation in non-coding exon 3 of the TMC1 gene in two ethnically related Iranian deaf families from different geographical regions; evidence for founder effect. Int J Pediatr Otorhinolaryngol, 77:821-826.
33. Reiisi S, Sanati MH, Tabatabaiefar MA et al (2014). The study of SLC26A4 gene causing autosomal recessive hearing loss by linkage analysis in a Cohort of Iranian Populations. Int J Mol Cell Med, 3:176-82.
34. Practice P, Committee G (2014). American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss. Genet Med, 16:347-355.
2. Masoudi M, Ahangari N, Zonouzi AAP et al (2016). Genetic Linkage Analysis of DFNB3, DFNB9 and DFNB21 Loci in GJB2 Negative Families with Autosomal Recessive Non-syndromic Hearing Loss. Iran J Public Health, 45:680-7.
3. Sanaz Arzhangi B, Kevin Booth B, Ahmad Daneshi M et al (2016). Heterogeneity of Hereditary Hearing Loss in Iran: a Comprehensive Review. Arch Iran Med, 19:720-728.
4. Chaleshtori MH, Zohour MM, Rad LH et al (2006). Autosomal recessive and sporadic non syndromic hearing loss and the incidence of Cx26 mutations in a Province of Iran. Iran J Public Health, 35:88-91.
5. Azadegan-Dehkordi F, Bahrami T, Shir-zad M et al (2019). Mutations in GJB2 as Major Causes of Autosomal Reces-sive Non-Syndromic Hearing Loss: First Report of c. 299-300delAT Mu-tation in Kurdish Population of Iran. J Audiol Otol, 23(1):20-26.
6. Saadat M (2005). Epidemiology and mortality of hospitalized burn patients in Kohkiluye va Boyerahmad province (Iran): 2002–2004. Burns, 31:306-309.
7. koohiyan M, Ahmadi A, koohian F et al (2019). An update of spectrum and frequency of GJB2 mutations causing hearing loss in the south of Iran: a literature review. Int J Pediatr Otorhinolaryngol, 119:136-140.
8. Koohiyan M, Chaleshtori MH, Salehi M et al (2018). GJB2 mutations causing autosomal recessive non-syndromic hearing loss (ARNSHL) in two Iranian populations: Report of two novel vari-ants. Int J Pediatr Otorhinolaryngol, 107:121-126.
9. Ghasemnejad T, Khaniani MS, Zarei F et al (2017). An update of common autosomal recessive non-syndromic hearing loss genes in Iranian population. Int J Pediatr Otorhinolaryngol, 97: 113-126.
10. Yan D, Xiang G, Chai X, Qing J et al (2017). Screening of deafness-causing DNA variants that are common in patients of European ancestry using a microarray-based approach. PloS one, 12:e0169219.
11. Lindner TH, Hoffmann K (2005). easyLINKAGE: a PERL script for easy and automated two-/multi-point linkage analyses. Bioinformatics, 21:405-407.
12. Fishelson M, Geiger D (2004). Optimizing exact genetic linkage computations. J Comput Biol, 11:263-275.
13. Koohiyan M (2019). A systematic review of SLC26A4 mutations causing hearing loss in the Iranian population. Int J Pediatr Otorhinolaryngol, 125:1-5.
14. Wu C-C, Lu Y-C, Chen P-J et al (2010). Phenotypic analyses and mutation screening of the SLC26A4 and FOXI1 genes in 101 Taiwanese families with bilateral nonsyndromic enlarged vestibular aqueduct (DFNB4) or Pendred syndrome. Audiol Neurootol, 15:57-66.
15. Kahrizi K, Mohseni M, Nishimura C et al (2009). Identification of SLC26A4 gene mutations in Iranian families with hereditary hearing impairment. Eur J Pediatr, 168:651-3.
16. Yazdanpanahi N, Tabatabaiefar MA, Farrokhi E et al (2013). Compound heterozygosity for two novel SLC26A4 mutations in a large Iranian pedigree with Pendred syndrome. Clin Exp Otorhinolaryngol, 6:201-208.
17. Hilgert N, Kahrizi K, Dieltjens N et al (2009). A large deletion in GPR98 causes type IIC Usher syndrome in male and female members of an Iranian family. J Med Genet, 46:272-276.
18. Tabatabaiefar M, Alasti F, Shariati L, Farrokhi E (2011). DFNB93, a novel locus for autosomal recessive moderate‐to‐severe hearing impairment. Clin Genet, 79:594-598.
19. Babanejad M, Fattahi Z, Bazazzadegan N et al (2012). A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran. Am J Med Genet Part A, 158:2485-2492.
20. Sloan-Heggen CM, Babanejad M, Beheshtian M et al (2015). Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran. J Med Genet, 52:823-829.
21. Friedman TB, Liang Y, Weber JL et al (1995). A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17. Nat genet, 9:86-91.
22. Cengiz FB, Duman D, Sırmacı A et al (2010). Recurrent and private MYO15A mutations are associated with deafness in the Turkish population. Genet Test Mol Biomarkers, 14:543-550.
23. Zarepour N, Koohiyan M, Taghipour-Sheshdeh A et al (2019). Identification and Clinical Implications of a Novel MYO15A Variant in a Consanguineous Iranian Family by Targeted Exome Sequencing. Audiol Neurootol , 24(1) :25-31.
24. Bashir R, Fatima A, Naz S (2012). Prioritized sequencing of the second exon of MYO15A reveals a new mutation segregating in a Pakistani family with moderate to severe hearing loss. Eur J Med Genet, 55:99-102.
25. Sadeghi A, Sanati MH, Alasti F et al (2009). 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 of Biotechnol, 7:108-111.
26. Choi BY, Ahmed ZM, Riazuddin S et al (2009). Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan. Clin genet, 75:237-243.
27. Chiu Y-H, Wu C-C, Lu Y-C et al (2010). Mutations in the OTOF gene in Taiwanese patients with auditory neuropathy. Audiol Neurootol, 15:364-374.
28. Tabatabaiefar M, Alasti F, Zohour MM et al (2011). Genetic linkage analysis of 15 DFNB loci in a group of Iranian families with autosomal recessive hearing loss. Iran J Public Health, 40:34-48.
29. Khosrofar M, Pourreza MR, Asgharzadeh S et al (2017). Genetic Linkage Analysis of the DFNB21 Locus in Autosomal Recessive Hearing Loss in Large Families from Khuzestan Province. Arak Medical University Journal, 20:31-38.
30. Schrauwen I, Helfmann S, Inagaki A et al (2012). A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment. Am J Med Genet, 91:636-645.
31. Kawashima Y, Géléoc GS, Kurima K et al (2011). Mechanotransduction in mouse inner ear hair cells requires transmembrane channel–like genes. J Clin Invest, 121:4796-809.
32. Davoudi-Dehaghani E, Zeinali S, Mahdieh N et al (2013). A transversion mutation in non-coding exon 3 of the TMC1 gene in two ethnically related Iranian deaf families from different geographical regions; evidence for founder effect. Int J Pediatr Otorhinolaryngol, 77:821-826.
33. Reiisi S, Sanati MH, Tabatabaiefar MA et al (2014). The study of SLC26A4 gene causing autosomal recessive hearing loss by linkage analysis in a Cohort of Iranian Populations. Int J Mol Cell Med, 3:176-82.
34. Practice P, Committee G (2014). American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss. Genet Med, 16:347-355.
| Files | ||
| Issue | Vol 48 No 9 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v48i9.3031 | |
| Keywords | ||
| Autosomal recessive non-syndromic hearing loss (ARNSHL); DFNB loci Homozygosity mapping Iran | ||
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How to Cite
1.
KOOHIYAN M, REIISI S, AZADEGAN-DEHKORDI F, SALEHI M, ABTAHI H, HASHEMZADEH-CHALESHTORI M, NOORI-DALOII MR, TABATABAIEFAR MA. Screening of 10 DFNB Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for GJB2 Mutations. Iran J Public Health. 2019;48(9):1704-1713.
