Identification of a Novel Frameshift Mutation in the TECTA Gene in an Iranian Family With Autosomal Nonsyndromic Hearing Loss
Abstract
Hearing loss (HL) is one of the most frequent birth defects, and genetic factors contribute to the pathogenesis of the disorder in about half of the patients. In the present study, we performed whole-exome sequencing (WES) based on Next-generation sequencing (NGS) in an Iranian family with hereditary HL. Then, Sanger sequencing was used to verify the segregation of the variant recognized in affected family members. A novel homozygous frameshift variation, c.649-650insC, in TECTA was found in the family, which might lead to a truncated TECTA protein (p. Asn218Gln fsX31). Our findings propose that the homozygous TECTA-p.N218QfsX31 mutation is the pathogenic variant for ARNSHL. To the best of our knowledge, this mutation has not been described in patients with the HL phenotype and so far has not to be reported in any of the mutation databases. Our data expand the spectrum of mutations in the TECTA gene in nonsyndromic hearing loss.
1. Talebi F, Mardasi FG, Asl JM, Tizno S, Zadeh MN. Identification of Novel PTPRQ and MYO1A Mutations in An Iranian Pedigree with Autosomal Recessive Hearing Loss. Cell J 2018;20:127-31.
2. Morton CC, Nance WE. Newborn hearing screening--a silent revolution. N Engl J Med 2006;354:2151-64.
3. Talebi F, Mardasi FG, Asl JM. Novel homozygous mutation in the MYO15A gene in autosomal recessive hearing loss. Zahedan J Resin Med Sci 2016;18:e4256.
4. Di Resta C, Galbiati S, Carrera P, Ferrari M. Next-generation sequencing approach for the diagnosis of human diseases: open challenges and new opportunities. EJIFCC. 2018;29:4-14.
5. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods2010;7:248-9.
6. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009;4:1073-81.
7. Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 2014;11:361-2.
8. Yamamoto N, Mutai H, Namba K, Morita N, Masuda S, Nishi Y, et al. Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss. Orphanet J Rare Dis 2017;12:157.
9. Tsai HT, Wang YP, Chung SF, Lin HC, Ho GM, Shu MT. A novel mutation in the WFS1 gene identified in a Taiwanese family with low-frequency hearing impairment. BMC Med Genet 2007;8:26.
10. Legan PK, Rau A, Keen JN, Richardson GP. The mouse tectorins. Modular matrix proteins of the inner ear homologous to components of the sperm-egg adhesion system. J BiolChem 1997;272:8791-801.
11. Verhoeven K, Van Camp G, Govaerts PJ, Balemans W, Schatteman I, Verstreken M, et al. A gene for autosomal dominant nonsyndromic hearing loss (DFNA12) maps to chromosome 11q22-24. Am J Hum Genet 1997;60:1168-73.
12. Verhoeven K, Van Laer L, Kirschhofer K, Legan PK, Hughes DC, Schatteman I, et al. Mutations in the human alpha-tectorin gene cause autosomal dominant nonsyndromic hearing impairment. Nat Genet. 1998;19:60-2.
13. Hughes DC, Legan PK, Steel KP, Richardson GP. Mapping of the alpha-tectorin gene (TECTA) to mouse chromosome 9 and human chromosome 11: a candidate for human autosomal dominant nonsyndromic deafness. Genomics 1998;48:46-51.
14. Legan PK, Goodyear RJ, Morín M, Mencia A, Pollard H, Olavarrieta L, et al. Three deaf mice: mouse models for TECTA-based human hereditary deafness reveal domainspecific structural phenotypes in the tectorial membrane. Hum Mol Genet 2013;23:2551-68.
15. Maeda Y, Fukushima K, Kasai N, Maeta M, Nishizaki K. Quantification of TECTA and DFNA5 expression in the developing mouse cochlea. Neuroreport 2001;12:3223-6.
16. Richardson GP, de Monvel JB, Petit C. How the genetics of deafness illuminates auditory physiology. Annu Rev Physiol 2011;73:311-34.
17. Rau A, Legan PK, Richardson GP. Tectorin mRNA expression is spatially and temporally restricted during mouse inner ear development. J Comp Neurol 1999;405:271-80.
18. Alasti F, Sanati MH, Behrouzifard AH, Sadeghi A, de Brouwer AP, Kremer H, et al. A novel TECTA mutation confirms the recognizable phenotype among autosomal recessive hearing impairment families.Int J PediatrOtorhinolaryngol 2008;72:249-55.
19. Meyer NC, Alasti F, Nishimura CJ, Imanirad P, Kahrizi K, Riazalhosseini Y, et al. Identification of three novel TECTA mutations in Iranian families with autosomal recessive nonsyndromic hearing impairment at the DFNB21 locus. Am J Med Genet A 2007;143A:1623-9.
20. Meyer NC, Nishimura CJ, McMordie S, Smith RJ. Audioprofiling identifies TECTA and GJB2-related deafness segregating in a single extended pedigree. Clin Genet 2007;72:130-7.
21. Hashemzadeh-Chaleshtori M, Saidijam M, Jami M-S, Ghasemi-Dehkordi P. MicroRNA-183 Family in Inner Ear: Hair Cell Development and Deafness. J AudiolOtol 2016;20:131-8.
22. Mustapha M, Weil D, Chardenoux S, Elias S, El-Zir E, Beckmann JS, et al. An α-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual nonsyndromic deafness, DFNB21. Hum Mol Genet 1999;8:409-12.
2. Morton CC, Nance WE. Newborn hearing screening--a silent revolution. N Engl J Med 2006;354:2151-64.
3. Talebi F, Mardasi FG, Asl JM. Novel homozygous mutation in the MYO15A gene in autosomal recessive hearing loss. Zahedan J Resin Med Sci 2016;18:e4256.
4. Di Resta C, Galbiati S, Carrera P, Ferrari M. Next-generation sequencing approach for the diagnosis of human diseases: open challenges and new opportunities. EJIFCC. 2018;29:4-14.
5. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods2010;7:248-9.
6. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009;4:1073-81.
7. Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 2014;11:361-2.
8. Yamamoto N, Mutai H, Namba K, Morita N, Masuda S, Nishi Y, et al. Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss. Orphanet J Rare Dis 2017;12:157.
9. Tsai HT, Wang YP, Chung SF, Lin HC, Ho GM, Shu MT. A novel mutation in the WFS1 gene identified in a Taiwanese family with low-frequency hearing impairment. BMC Med Genet 2007;8:26.
10. Legan PK, Rau A, Keen JN, Richardson GP. The mouse tectorins. Modular matrix proteins of the inner ear homologous to components of the sperm-egg adhesion system. J BiolChem 1997;272:8791-801.
11. Verhoeven K, Van Camp G, Govaerts PJ, Balemans W, Schatteman I, Verstreken M, et al. A gene for autosomal dominant nonsyndromic hearing loss (DFNA12) maps to chromosome 11q22-24. Am J Hum Genet 1997;60:1168-73.
12. Verhoeven K, Van Laer L, Kirschhofer K, Legan PK, Hughes DC, Schatteman I, et al. Mutations in the human alpha-tectorin gene cause autosomal dominant nonsyndromic hearing impairment. Nat Genet. 1998;19:60-2.
13. Hughes DC, Legan PK, Steel KP, Richardson GP. Mapping of the alpha-tectorin gene (TECTA) to mouse chromosome 9 and human chromosome 11: a candidate for human autosomal dominant nonsyndromic deafness. Genomics 1998;48:46-51.
14. Legan PK, Goodyear RJ, Morín M, Mencia A, Pollard H, Olavarrieta L, et al. Three deaf mice: mouse models for TECTA-based human hereditary deafness reveal domainspecific structural phenotypes in the tectorial membrane. Hum Mol Genet 2013;23:2551-68.
15. Maeda Y, Fukushima K, Kasai N, Maeta M, Nishizaki K. Quantification of TECTA and DFNA5 expression in the developing mouse cochlea. Neuroreport 2001;12:3223-6.
16. Richardson GP, de Monvel JB, Petit C. How the genetics of deafness illuminates auditory physiology. Annu Rev Physiol 2011;73:311-34.
17. Rau A, Legan PK, Richardson GP. Tectorin mRNA expression is spatially and temporally restricted during mouse inner ear development. J Comp Neurol 1999;405:271-80.
18. Alasti F, Sanati MH, Behrouzifard AH, Sadeghi A, de Brouwer AP, Kremer H, et al. A novel TECTA mutation confirms the recognizable phenotype among autosomal recessive hearing impairment families.Int J PediatrOtorhinolaryngol 2008;72:249-55.
19. Meyer NC, Alasti F, Nishimura CJ, Imanirad P, Kahrizi K, Riazalhosseini Y, et al. Identification of three novel TECTA mutations in Iranian families with autosomal recessive nonsyndromic hearing impairment at the DFNB21 locus. Am J Med Genet A 2007;143A:1623-9.
20. Meyer NC, Nishimura CJ, McMordie S, Smith RJ. Audioprofiling identifies TECTA and GJB2-related deafness segregating in a single extended pedigree. Clin Genet 2007;72:130-7.
21. Hashemzadeh-Chaleshtori M, Saidijam M, Jami M-S, Ghasemi-Dehkordi P. MicroRNA-183 Family in Inner Ear: Hair Cell Development and Deafness. J AudiolOtol 2016;20:131-8.
22. Mustapha M, Weil D, Chardenoux S, Elias S, El-Zir E, Beckmann JS, et al. An α-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual nonsyndromic deafness, DFNB21. Hum Mol Genet 1999;8:409-12.
| Files | ||
| Issue | Vol 59, No 3 (2021) | |
| Section | Case Report(s) | |
| DOI | https://doi.org/10.18502/acta.v59i3.5790 | |
| Keywords | ||
| TECTA Hearing loss Novel mutation Next-Generation sequencing (NGS) | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mohammadi-Asl J, Saki N, Karimi M, Ghanbari Mardasi F. Identification of a Novel Frameshift Mutation in the TECTA Gene in an Iranian Family With Autosomal Nonsyndromic Hearing Loss. Acta Med Iran. 2021;59(3):177-181.
