Brief Report of Variants Detected in Hereditary Hearing Loss Cases in Iran over a 3-Year Period
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.
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.
|Issue||Vol 48 No 10 (2019)|
|OtoSCOPE Hereditary hearing loss Novel variant Known variant|
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