The worldwide frequency of MYO15A gene mutations in patients with autosomal recessive non-syndromic hearing loss: A meta‐analysis

Document Type: Review Article

Authors

1 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Education Development Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Pharmaceutical Research Center, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

7 Department of Medical Genetics, Tabriz University of Medical Sciences, Tabriz, Iran

8 Ibn Sina Medical Genetic Diagnostic Laboratory, Tabriz University of Medical Sciences, Tabriz, Iran

9 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

10 Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

MYO15A is the third most crucial gene in hereditary sensorineural hearing loss after GJB2 and SLC26A4. In the present study, we reviewed the prevalence of MYO15A mutations in patients with autosomal recessive non-syndromic hearing loss (ARNSHL). In this meta-analysis, we conducted a search of PubMed, Web of Science, Excerpta Medica Database, and Scopus, and identified the articles up to September 2019 without any time limit. Two investigators independently selected the relevant papers and extracted the required information. A total of 44 case-control and case series studies were considered, and 4176 patients and 3706 healthy individuals, as the control group, were included. The pooled frequency of MYO15A mutations between patients suffering from ARNSHL was calculated as 6.2% (95% CI: 4.9-7.8, P-value<0.001). There was heterogeneity between our studies (P-value<0.001, I2=58.1%); therefore, the random-effects model was utilized for analysis. Given the results, in many countries, the MYO15A gene had a significant contribution to hearing loss. Moreover, in several regions, specific dominant mutations in this gene have been reported. Therefore, the ethnic background should be considered to investigate the mutations of the MYO15A gene.

Keywords


1. Atik T, Onay H, Aykut A, Bademci G, Kirazli T, Tekin M, et al. Comprehensive analysis of deafness genes in families with autosomal recessive nonsyndromic hearing loss. PLoS One 2015; 10-21.
2. Yan D, Tekin D, Bademci G, Foster J, 2nd, Cengiz FB, Kannan-Sundhari A, et al. Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents. Hum Genet 2016; 135:953-961.
3. Mahdieh N, Rabbani B, Wiley S, Akbari MT, Zeinali S. Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations. J Hum Genet 2010; 55:639-648.
4. Miyagawa M, Nishio SY, Hattori M, Moteki H, Kobayashi Y, Sato H, et al. Mutations in the MYO15A gene are a significant cause of nonsyndromic hearing loss: Massively parallel DNA sequencing-based analysis. Ann Otol Rhinol Laryngol 2015; 124:158S-168S.
5. Rabbani B, Tekin M, Mahdieh N. The promise of whole-exome sequencing in medical genetics. J Hum Genet 2014; 59:5-15.
6. Hofrichter MAH, Mojarad M, Doll J, Grimm C, Eslahi A, Hosseini NS, et al. The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: Evidence from a consanguineous Iranian family. BMC Med Genet 2018; 19:81-91.
7. Alimardani M, Hosseini SM, Khaniani MS, Haghi MR, Eslahi A, Farjami M, et al. Targeted mutation analysis of the SLC26A4, MYO6, PJVK and CDH23 genes in Iranian patients with AR nonsyndromic hearing loss. Fetal Pediatr Pathol 2019; 38:93-102.
8. Yan D, Tekin D, Bademci G, Foster J, Cengiz FB, Kannan-Sundhari A, et al. Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents. Hum Genet 2016; 135:953-961.
9. Masoudi M, Ahangari N, Zonouzi AAP, Zonouzi AP, Nejatizadeh A. Genetic linkage analysis of DFNB3, DFNB9 and DFNB21 loci in GJB2 negative families with autosomal recessive non-syndromic hearing loss. Iran J Public Health 2016; 45:680-687.
10. Palombo F, Al-Wardy N, Ruscone GAG, Oppo M, Al Kindi MN, Angius A, et al. A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman. J Hum Genet 2017; 62:259-264.
11. Rehman AU, Bird JE, Faridi R, Shahzad M, Shah S, Lee K, et al. Mutational spectrum of MYO15A and the molecular mechanisms of DFNB3 human deafness. Hum Mutat 2016; 37:991-1003.
12. Reiisi S, Tabatabaiefar MA, Sanati MH, Chaleshtori MH. Screening of DFNB3 in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh4 domain of the MYO15A gene in a linked family. Iran J Basic Med Sci 2016; 19:772-778.
13. Shearer AE, Hildebrand MS, Webster JA, Kahrizi K, Meyer NC, Jalalvand K, et al. Mutations in the first MyTH4 domain of MY015A are a common cause of DFNB3 hearing loss. Laryngoscope 2009; 119:727-733.
14. Hoy D, Brooks P, Woolf A, Blyth F, March L, Bain C, et al. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. J Clin Epidemiol 2012; 65:934-939.
15. Subaşıoğlu A. Research of genetic bases of hereditary non-syndromic hearing loss. Turk Pediatri Ars;122-133.
16. 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; 40:34-48.
17. Miyagawa M, Nishio Sy, Ikeda T, Fukushima K, Usami Si. Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS. PLoS One 2013; 8:e75793.
18. Manzoli GN, Bademci G, Acosta AX, Felix TM, Cengiz FB, Foster J, et al. Targeted resequencing of deafness genes reveals a founder MYO15A variant in northeastern Brazil. Ann Hum Genet 2016; 80:327-331.
19. Tsukada K, Nishio Sy, Hattori M, Usami Si. Ethnic-specific spectrum of GJB2 and SLC26A4 mutations: Their origin and a literature review. Ann Otol Rhinol Laryngol 2015; 124:61S-76S.
20.   http://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=MYO15A
21. Yan D, Kannan-Sundhari A, Vishwanath S, Qing J, Mittal R, Kameswaran M, et al. The genetic basis of nonsyndromic hearing loss in Indian and Pakistani populations. Genet Test Mol Biomarkers 2015; 19:512-527.
22. Sommen M, Schrauwen I, Vandeweyer G, Boeckx N, Corneveaux JJ, van den Ende J, et al. DNA diagnostics of hereditary hearing loss: A targeted resequencing approach combined with a mutation classification system. Hum Mutat 2016; 37:812-819.
23. Brownstein Z, Friedman LM, Shahin H, Oron-Karni V, Kol N, Abu Rayyan A, et al. Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in Middle Eastern families. Genome Biol 2011; 12:R89.
24. Yang T, Wei X, Chai Y, Li L, Wu H. Genetic etiology study of the non-syndromic deafness in Chinese Hans by targeted next-generation sequencing. Orphanet J Rare Dis 2013; 8:85-93.
25. Nal N, Ahmed ZM, Erkal E, Alper ÖM, Lüleci G, Dinç O, et al. Mutational spectrum of MYO15A: The large N-terminal extension of myosin XVA is required for hearing. Hum Mutat 2007; 28:1014-1019.
26. Miyagawa M, Naito T, Nishio SY, Kamatani N, Usami S. Targeted exon sequencing successfully discovers rare causative genes and clarifies the molecular epidemiology of Japanese deafness patients. PLoS One 2013; 8:e71381.
27. Cengiz FB, Duman D, Sirmaci A, Tokgöz-Yilmaz S, Erbek S, Öztürkmen-Akay H, et al. Recurrent and private MYO15A mutations are associated with deafness in the Turkish population. Genet Test Mol Biomarkers 2010; 14:543-550.
28. Palombo F, Al-Wardy N, Ruscone GA, Oppo M, Kindi MN, Angius A, et al. A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman. J Hum Genet 2017; 62:259-264.
29. Sloan-Heggen CM, Babanejad M, Beheshtian M, Simpson AC, Booth KT, Ardalani F, et al. Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran. J Med Genet 2015; 52:823-829.
30. Duman D, Sirmaci A, Cengiz FB, Ozdag H, Tekin M. Screening of 38 genes identifies mutations in 62% of families with nonsyndromic deafness in Turkey. Genet Test Mol Biomarkers 2011; 15:29-33.
31. 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; 14:543-550.
32. Naz S, Imtiaz A, Mujtaba G, Maqsood A, Bashir R, Bukhari I, et al. Genetic causes of moderate to severe hearing loss point to modifiers. Clin Genet 2017; 91:589-598.
33. Bashir R, Fatima A, Naz S. 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 2012; 55:99-102.
34. 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; 109:535-541.
35. Kalay E, Uzumcu A, Krieger E, Caylan R, Uyguner O, Ulubil-Emiroglu M, et al. MY015A (DFNB3) mutations in Turkish hearing loss families and functional modeling of a novel motor domain mutation. Am J Med Genet A 2007; 143A:2382-2389.
36. Sadeghi A, Sanati MH, Alasti F, Chaleshtori MH, 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 Biotechnol 2009; 7:108-111+120.
37. Belguith H, Aifa-Hmani M, Dhouib H, Said MB, Mosrati MA, Lahmar I, et al. Screening of the DFNB3 locus: identification of three novel mutations of MYO15A associated with hearing loss and further suggestion for two distinctive genes on this locus. Genet Test Mol Biomarkers 2009; 13:147-151.
38. Shahin H, Walsh T, Abu Rayyan A, Lee MK, Higgins J, Dickel D, et al. Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families. Eur J Hum Genet 2010; 18:407-413.
39. Diaz-Horta O, Duman D, Foster J, 2nd, Sirmaci A, Gonzalez M, Mahdieh N, et al. Whole-exome sequencing efficiently detects rare mutations in autosomal recessive nonsyndromic hearing loss. PLoS One 2012; 7:e50628.
40. 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:1857-1864.
41. Woo HM, Park HJ, Baek JI, Park MH, Kim UK, Sagong B, et al. Whole-exome sequencing identifies MYO15A mutations as a cause of autosomal recessive nonsyndromic hearing loss in Korean families. BMC Med Genet 2013; 14:72.
42. Brownstein Z, Abu-Rayyan A, Karfunkel-Doron D, Sirigu S, Davidov B, Shohat M, et al. Novel myosin mutations for hereditary hearing loss revealed by targeted genomic capture and massively parallel sequencing. Eur J Hum Genet 2014; 22:768-775.
43. Shafique S, Siddiqi S, Schraders M, Oostrik J, Ayub H, Bilal A, et al. Genetic spectrum of autosomal recessive non-syndromic hearing loss in Pakistani families. PLoS One 2014; 9-19.
44. Vona B, Müller T, Nanda I, Neuner C, Hofrichter MAH, Schröder J, et al. Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations. Genet Med 2014; 16:945-953.
45. Atik T, Onay H, Aykut A, Bademci G, Kirazli T, Tekin M, et al. Comprehensive analysis of deafness genes in families with autosomal recessive nonsyndromic hearing Loss. PLoS One 2015; 10:e0142154.
46. Gu X, Guo L, Ji H, Sun S, Chai R, Wang L, et al. Genetic testing for sporadic hearing loss using targeted massively parallel sequencing identifies 10 novel mutations. Clin Genet 2015; 87:588-593.
47. Ammar‐Khodja F, Bonnet C, Dahmani M, Ouhab S, Lefèvre GM, Ibrahim H, et al. Diversity of the causal genes in hearing impaired Algerian individuals identified by whole exome sequencing. Mol Genet Genomic Med 2015; 3:189-196.
48. Asgharzade S, Chaleshtori MH, Tabatabaifar MA, Reisi S, Modaressi MH. Mutation in second exon of myo15a gene cause of nonsyndromic hearing loss and its association in the Arab population in Iran. Genetika 2016; 48:587-596.
49. Moteki H, Azaiez H, Booth KT, Shearer AE, Sloan CM, Kolbe DL, et al. Comprehensive genetic testing with ethnic‐specific filtering by allele frequency in a Japanese hearing‐loss population. Clin Genet 2016; 89:466-472.
50. Jung J, Lee JS, Cho KJ, Yu S, Yoon JH, Gee HY, et al. Genetic predisposition to sporadic congenital hearing loss in a pediatric population. Sci Rep 2017; 7-16.
51. Salime S, Charif M, Bousfiha A, Elrharchi S, Bakhchane A, Charoute H, et al. Homozygous mutations in PJVK and MYO15A genes associated with non-syndromic hearing loss in Moroccan families. Int J Pediatr Otorhinolaryngol 2017; 101:25-29.
52. Baux D, Vaché C, Blanchet C, Willems M, Baudoin C, Moclyn M, et al. Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients. Sci Rep 2017; 7:16783-16793.
53. Cabanillas R, Dineiro M, Cifuentes GA, Castillo D, Pruneda PC, Alvarez R, et al. Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients. BMC Med Genomics 2018; 11-28.
54. Chen Y, Lu Y, Kuyaxi P, Cheng J, Zhao J, Zhao Q, et al. Identification of pathogenic genes of nonsyndromic hearing loss in Uyghur families using massively parallel DNA sequencing technique. Dis Markers 2018.
55. Danial-Farran N, Brownstein Z, Gulsuner S, Tammer L, Khayat M, Aleme O, et al. Genetics of hearing loss in the Arab population of Northern Israel. Eur J Hum Genet 2018; 26:1840-1847.
56. Guan Q, Balciuniene J, Cao K, Fan Z, Biswas S, Wilkens A, et al. AUDIOME: a tiered exome sequencing–based comprehensive gene panel for the diagnosis of heterogeneous nonsyndromic sensorineural hearing loss. Genet Med 2018; 20:1600-1608.
57. He L, Pang X, Liu H, Chai Y, Wu H, Yang T. Targeted next-generation sequencing and parental genotyping in sporadic Chinese Han deaf patients. Clin Genet 2018; 93:899-904.
58. Han JJ, Nguyen PD, Oh DY, Han JH, Kim AR, Kim MY, et al. Elucidation of the unique mutation spectrum of severe hearing loss in a Vietnamese pediatric population. Sci Rep 2019; 9-18.
59. Khan A, Han S, Wang R, Ansar M, Ahmad W, Zhang X. Sequence variants in genes causing nonsyndromic hearing loss in a Pakistani cohort. Mol Genet Genomic Med 2019:e917.
60. Liu WH, Chang PY, Chang SC, Lu JJ, Wu CM. Mutation screening in non-syndromic hearing loss patients with cochlear implantation by massive parallel sequencing in Taiwan. PLoS One 2019; 14-29.
61. Mehregan H, Mohseni M, Jalalvand K, Arzhangi S, Nikzat N, Banihashemi S, et al. Novel mutations in MYTH4-FERM domains of myosin 15 are associated with autosomal recessive nonsyndromic hearing loss. Int J Pediatr Otorhinolaryngol 2019; 117:115-126.
62. Sang SS, Ling J, Liu XZ, Mei LY, Cai XZ, Li TX, et al. Proband whole-exome sequencing identified genes responsible for autosomal recessive non-syndromic hearing loss in 33 Chinese nuclear families. Front Genet 2019; 10-20.