Brief Report of Variants Detected in Hereditary Hearing Loss Cases in Iran over a 3-Year Period
-
Niloofar BAZAZZADEGAN
,
Raheleh VAZEHAN
,
Mahsa FADAEE
,
Zohreh FATTAHI
,
Ayda ABOLHASSANI
,
Elham PARSIMEHR
,
Zahra KALHOR
,
Mehrshid FARAJI ZONOOZ
,
Fatemeh AHANGARI
,
Shima DEHDAHSI
,
Farshide SAMIEE
,
Payman JAMALI
,
Haleh HABIBI
,
Younes NOURIZADEH
,
Shokouh MAHDAVI
,
Maryam BEHESHTIAN
,
Ariana KARIMINEJAD
,
Richard JH SMITH
,
Hossein NAJMABADI
Abstract
Background: Diagnosis of hereditary hearing loss (HHL) as a heterogeneous disorder is very important espe-cially in countries with high rates of consanguinity where the autosomal recessive pattern of inheritance is preva-lent. Techniques such as next-generation sequencing, a comprehensive genetic test using targeted genomic en-richment and massively parallel sequencing (TGE + MPS), have made the diagnosis more cost-effective. The aim of this study was to determine HHL variants with comprehensive genetic testing in our country.
Methods: Fifty GJB2 negative individuals with HHL were referred to the Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, one of the reference diagnostic genetic laboratories in Iran, during a 3-year period between 2014 and 2017. They were screened with the OtoSCOPE test, the targeted genomic enrichment and massively parallel sequencing (TGE + MPS) platform after a detailed history had been taken along with clinical evaluation.
Results: Among 32 out of 50 GJB2 negative patients (64%), 34 known pathogenic and novel variants were de-tected of which 16 (47%) were novel, identified in 10 genes of which the most prevalent were CDH23, MYO7A and MYO15A.
Conclusion: These results provide a foundation from which to make appropriate recommendations for the use of comprehensive genetic testing in the evaluation of Iranian patients with hereditary hearing loss.
1. Smith R, Green G, Camp G (1999). Hereditary hearing loss and deafness overview. https://www.medschool.lsuhsc.edu/pediatrics/docs/Deafness%20and%20Hereditary%20Hearing%20Loss%20Overview.pdf. Retrieved March, 13 1999.
2. Saadat M, Ansari-Lari M and Farhud D (2004). Short report consanguineous marriage in Iran. Ann Hum Biol, 31 (2): 263-269.
3. Sloan-Heggen CM, Babanejad M et al (2015). Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran. J Med Genet, 52 (12): 823-829.
4. Bazazzadegan N, Nikzat N, Fattahi Z et al (2012). The spectrum of GJB2 mutations in the Iranian population with non-syndromic hearing loss—a twelve year study. Int J pediatr Otorhinolaryngol, 76 (8): 1164-1174.
5. Hashemzadeh Chaleshtori M, Farhud DD et al (2008). Molecular Pathology of 6 Novel GJB2 Allelic Variants Detected in Familial and Sporadic Iranian Non Syndromic Hearing Loss Cases. Iran J Public Health, 37(3):9-18.
6. Hashemzadeh Chaleshtori M, Montazer Zohour M 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(1):88-91.
7. Beheshtian Maryam, Babanejad Mojgan, Azaiez Hela et al (2016). Heterogeneity of Hereditary Hearing Loss in Iran: a Comprehensive Review. Arch Iran Med, 19 (10): 720-728.
8. Smith Rjh Fau - Shearer AE, Shearer Ae Fau - Hildebrand MS, Hildebrand Ms Fau - Van Camp G and Van Camp G (2014). Deafness and Hereditary Hearing Loss Overview BTI - GeneReviews(R).
9. Shearer AE, DeLuca AP, Hildebrand MS et al (2010). Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing. Proc Natl Acad Sci USA, 107 (49): 21104-21109.
10. Yoshimura H, Iwasaki S, Nishio S-y et al (2014). Massively parallel DNA sequencing facilitates diagnosis of patients with Usher syndrome type 1. PLoS One, 9(3): e90688.
11. Cremers FP, Kimberling WJ, Külm M et al (2007). Development of a genotyping microarray for Usher syndrome. J Med Genet, 44 (2): 153-160.
12. Sommen M, Schrauwen I, Vandeweyer G et al (2016). DNA diagnostics of hereditary hearing loss: a targeted resequencing approach combined with a mutation classification system. Hum Mutat, 37 (8): 812-819.
13. Seco CZ, Wesdorp M, Feenstra I et al (2017). The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands. Eur J Hum Genet, 25 (3): 308-314.
14. Sloan-Heggen CM, Bierer AO, Shearer AE et al (2016). Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. Hum Genet, 135 (4): 441-450.
15. Fattahi Z, Shearer AE, Babanejad M et al (2012). Screening for MYO15A gene mutations in autosomal recessive nonsyndromic, GJB2 negative Iranian deaf population. Am J Med Genet A, 158 (8): 1857-1864.
16. Stabej PLQ, Saihan Z, Rangesh N et al (2012). Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study. J Med Genet, 49 (1): 27-36.
17. Pierrache LH, Hartel BP, Van Wijk E et al (2016). Visual prognosis in USH2A-associated retinitis pigmentosa is worse for patients with Usher syndrome type IIa than for those with nonsyndromic Retinitis Pigmentosa. Ophthalmology, 123 (5): 1151-1160.
18. Delmaghani S, Aghaie A, Bouyacoub Y et al (2016). Mutations in CDC14A, encoding a protein phosphatase involved in hair cell ciliogenesis, cause autosomal-recessive severe to profound deafness. Am J Hum Genet, 98 (6): 1266-1270.
19. Mahdieh N, Shirkavand A, Rabbani B et al (2012). Screening of OTOF mutations in Iran: a novel mutation and review. Int J Pediatr Otorhinolaryngol, 76 (11): 1610-1615.
20. Van Hauwe P, Everett LA, Coucke P et al (1998). Two frequent missense mutations in Pendred syndrome. Hum Mol Genet, 7 (7): 1099-1104.
21. 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 (4): 201-208.
22. Zong L, Guan J, Ealy M et al (2015). Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder. J Med Genet, 52(8):523-31.
23. Masmoudi S, Antonarakis SE, Schwede T et al (2001). Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness. Hum Mut, 18 (2): 101-108.
24. Riazuddin S, Ahmed ZM, Fanning AS et al (2006). Tricellulin is a tight-junction protein necessary for hearing. Am J Hum Genet, 79 (6): 1040-1051.
25. Nobukuni Y, Watanabe A, Takeda K et al (1996). Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A. Am J Human Genet, 59 (1): 76-83.
26. Lenarduzzi S, Vozzi D, Morgan A et al (2015). Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis. Hear Res, 320 18-23.
27. 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 (1): 86-91.
28. Shearer AE, Hildebrand MS, Webster JA et al (2009). Mutations in the first MyTH4 domain of MYO15A are a common cause of DFNB3 hearing loss. Laryngoscope, 119 (4): 727-733.
29. 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 A, 158 (10): 2485-2492.
30. Read AP, Newton VE (1997). Waardenburg syndrome. J Med Genet, 34 (8): 656-665.
31. Jalilian N, Tabatabaiefar MA, Farhadi M et al (2015). Molecular and clinical characterization of Waardenburg syndrome type I in an Iranian cohort with two novel PAX3 mutations. Gene, 574 (2): 302-307.
32. Shearer AE, Smith RJ (2015). Massively parallel sequencing for genetic diagnosis of hearing loss: the new standard of care. Otolaryngol Head Neck Surg, 153 (2): 175-182.
33. Najmabadi H, Kahrizi K (2014). Genetics of non-syndromic hearing loss in the Middle East. Int J Pediatr Otorhinolaryngol, 78 (12): 2026-2036.
2. Saadat M, Ansari-Lari M and Farhud D (2004). Short report consanguineous marriage in Iran. Ann Hum Biol, 31 (2): 263-269.
3. Sloan-Heggen CM, Babanejad M et al (2015). Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran. J Med Genet, 52 (12): 823-829.
4. Bazazzadegan N, Nikzat N, Fattahi Z et al (2012). The spectrum of GJB2 mutations in the Iranian population with non-syndromic hearing loss—a twelve year study. Int J pediatr Otorhinolaryngol, 76 (8): 1164-1174.
5. Hashemzadeh Chaleshtori M, Farhud DD et al (2008). Molecular Pathology of 6 Novel GJB2 Allelic Variants Detected in Familial and Sporadic Iranian Non Syndromic Hearing Loss Cases. Iran J Public Health, 37(3):9-18.
6. Hashemzadeh Chaleshtori M, Montazer Zohour M 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(1):88-91.
7. Beheshtian Maryam, Babanejad Mojgan, Azaiez Hela et al (2016). Heterogeneity of Hereditary Hearing Loss in Iran: a Comprehensive Review. Arch Iran Med, 19 (10): 720-728.
8. Smith Rjh Fau - Shearer AE, Shearer Ae Fau - Hildebrand MS, Hildebrand Ms Fau - Van Camp G and Van Camp G (2014). Deafness and Hereditary Hearing Loss Overview BTI - GeneReviews(R).
9. Shearer AE, DeLuca AP, Hildebrand MS et al (2010). Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing. Proc Natl Acad Sci USA, 107 (49): 21104-21109.
10. Yoshimura H, Iwasaki S, Nishio S-y et al (2014). Massively parallel DNA sequencing facilitates diagnosis of patients with Usher syndrome type 1. PLoS One, 9(3): e90688.
11. Cremers FP, Kimberling WJ, Külm M et al (2007). Development of a genotyping microarray for Usher syndrome. J Med Genet, 44 (2): 153-160.
12. Sommen M, Schrauwen I, Vandeweyer G et al (2016). DNA diagnostics of hereditary hearing loss: a targeted resequencing approach combined with a mutation classification system. Hum Mutat, 37 (8): 812-819.
13. Seco CZ, Wesdorp M, Feenstra I et al (2017). The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands. Eur J Hum Genet, 25 (3): 308-314.
14. Sloan-Heggen CM, Bierer AO, Shearer AE et al (2016). Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. Hum Genet, 135 (4): 441-450.
15. Fattahi Z, Shearer AE, Babanejad M et al (2012). Screening for MYO15A gene mutations in autosomal recessive nonsyndromic, GJB2 negative Iranian deaf population. Am J Med Genet A, 158 (8): 1857-1864.
16. Stabej PLQ, Saihan Z, Rangesh N et al (2012). Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study. J Med Genet, 49 (1): 27-36.
17. Pierrache LH, Hartel BP, Van Wijk E et al (2016). Visual prognosis in USH2A-associated retinitis pigmentosa is worse for patients with Usher syndrome type IIa than for those with nonsyndromic Retinitis Pigmentosa. Ophthalmology, 123 (5): 1151-1160.
18. Delmaghani S, Aghaie A, Bouyacoub Y et al (2016). Mutations in CDC14A, encoding a protein phosphatase involved in hair cell ciliogenesis, cause autosomal-recessive severe to profound deafness. Am J Hum Genet, 98 (6): 1266-1270.
19. Mahdieh N, Shirkavand A, Rabbani B et al (2012). Screening of OTOF mutations in Iran: a novel mutation and review. Int J Pediatr Otorhinolaryngol, 76 (11): 1610-1615.
20. Van Hauwe P, Everett LA, Coucke P et al (1998). Two frequent missense mutations in Pendred syndrome. Hum Mol Genet, 7 (7): 1099-1104.
21. 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 (4): 201-208.
22. Zong L, Guan J, Ealy M et al (2015). Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder. J Med Genet, 52(8):523-31.
23. Masmoudi S, Antonarakis SE, Schwede T et al (2001). Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness. Hum Mut, 18 (2): 101-108.
24. Riazuddin S, Ahmed ZM, Fanning AS et al (2006). Tricellulin is a tight-junction protein necessary for hearing. Am J Hum Genet, 79 (6): 1040-1051.
25. Nobukuni Y, Watanabe A, Takeda K et al (1996). Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A. Am J Human Genet, 59 (1): 76-83.
26. Lenarduzzi S, Vozzi D, Morgan A et al (2015). Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis. Hear Res, 320 18-23.
27. 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 (1): 86-91.
28. Shearer AE, Hildebrand MS, Webster JA et al (2009). Mutations in the first MyTH4 domain of MYO15A are a common cause of DFNB3 hearing loss. Laryngoscope, 119 (4): 727-733.
29. 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 A, 158 (10): 2485-2492.
30. Read AP, Newton VE (1997). Waardenburg syndrome. J Med Genet, 34 (8): 656-665.
31. Jalilian N, Tabatabaiefar MA, Farhadi M et al (2015). Molecular and clinical characterization of Waardenburg syndrome type I in an Iranian cohort with two novel PAX3 mutations. Gene, 574 (2): 302-307.
32. Shearer AE, Smith RJ (2015). Massively parallel sequencing for genetic diagnosis of hearing loss: the new standard of care. Otolaryngol Head Neck Surg, 153 (2): 175-182.
33. Najmabadi H, Kahrizi K (2014). Genetics of non-syndromic hearing loss in the Middle East. Int J Pediatr Otorhinolaryngol, 78 (12): 2026-2036.
| Files | ||
| Issue | Vol 48 No 10 (2019) | |
| Section | Short Communication(s) | |
| DOI | https://doi.org/10.18502/ijph.v48i10.3500 | |
| Keywords | ||
| OtoSCOPE Hereditary hearing loss Novel variant Known variant | ||
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How to Cite
1.
BAZAZZADEGAN N, VAZEHAN R, FADAEE M, FATTAHI Z, ABOLHASSANI A, PARSIMEHR E, KALHOR Z, FARAJI ZONOOZ M, AHANGARI F, DEHDAHSI S, SAMIEE F, JAMALI P, HABIBI H, NOURIZADEH Y, MAHDAVI S, BEHESHTIAN M, KARIMINEJAD A, SMITH RJ, NAJMABADI H. Brief Report of Variants Detected in Hereditary Hearing Loss Cases in Iran over a 3-Year Period. Iran J Public Health. 2019;48(10):1910-1915.
