A Novel Deleterious MYO15A Gene Mutation Causes Nonsyndromic Hearing Loss

Document Type : Case Report


1 Department of Genetics, Khuzestan Science and Research Branch, Islamic Azad University, Ahvaz, Iran. Department of Genetics, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran.

2 Department of Biology, College of Science, University of Basrah, Basrah, Iraq.

3 Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.



Hearing loss (HL) is the most frequent sensory neurodeficiency, affecting a broad spectrum of individuals globally. Within this context, the role of genetic factors takes center stage, particularly in cases of hereditary HL.
Case Report:
Here, we present a nonsyndromic HL (NSHL) case report. The patient is a 21-year-old man with progressive HL. The whole-exome sequencing (WES) demonstrated a novel homozygous missense mutation, c.9908A>C; p.Lys3303Thr, in the proband's exon 61 of the MYO15A gene. Further analysis has revealed that the detected mutation is present in a heterozygous state in the parents.
WES analysis in this study revealed a novel mutation in the MYO15A gene. Our data indicates that the MYO15A-p.Lys3303Thr mutation is the likely pathogenic variant associated with NSHL. Additionally, this finding enhances genetic counseling for individuals with NSHL patients, highlighting the value of the WES method in detecting rare genetic variants.


Main Subjects

  1. Deafness and hearing loss [Internet]. [cited 2023 Dec 17]. Available from: https://www.who.int/news-room/fact-sheets/detail/deafness-and-hearing-loss
  2. 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. doi:10.18502/acta. v59i3.5790
  3. Mohammadi-Asl J, Saki N, Dehdashtiyan M, Neissi M, Ghanbari Mardasi F. Identification of a Novel WFS1 Mutation Using the Whole Exome Sequencing in an Iranian Pedigree with Autosomal Dominant Hearing Loss. Iran J Otorhinolaryngol. 2021 May;33(116):173-176. doi: 10.22038/ijorl. 2021.48471.2602
  4. Neissi M, Abdulzahra HKh, Sheikh-Hosseini M, Mabudi H, Mohammadi-Asl J, Al-Badran RA. Homozygous LOXHD1 Nonsense Mutation (c.1787G>A; p.W596X) is Associated with Hearing Loss in an Iranian Family: A Case Report. Int J Biomed. 2022;12(1):164-166. doi: 10.21103/ Article12(1)_CR
  5. Hilgert N, Smith RJH, Van Camp G. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat Res. 2009 Mar-Jun;681(2-3):189-196. doi: 10.1016/j.mrrev.2008.08.002
  6. Dixon PR, Feeny D, Tomlinson G, Cushing S, Chen JM, Krahn MD. Health-Related Quality of Life Changes Associated with Hearing Loss. JAMA Otolaryngol Head Neck Surg. 2020 Jul 1;146(7):630-638. doi: 10.1001/jamaoto.2020.0674
  7. Griffiths TD, Lad M, Kumar S, Holmes E, McMurray B, Maguire EA, et al. How Can Hearing Loss Cause Dementia? Neuron. 2020 Nov 11; 108(3): 401-412. doi: 10.1016/j.neuron. 2020. 08. 003
  8. Lee W, Chang Y, Shin H, Ryu S. Hearing Loss and Risk of Overall, Injury-Related, and Cardiovascular Mortality: The Kangbuk Samsung Health Study. J Clin Med. 2020 May 10;9(5):1415. doi: 10.3390/jcm9051415
  9. Aldè M, Cantarella G, Zanetti D, Pignataro L, La Mantia I, Maiolino L, et al. Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review. Biomedicines. 2023 Jun 1;11(6):1616. doi: 10.3390/ biomedicines11061616
  10. HGMD® home page [Internet]. [cited 2023 Dec 17]. Available from: https://www.hgmd. cf.ac.uk/ ac/i ndex.php
  11. Anderson DW, Probst FJ, Belyantseva IA, Fridell RA, Beyer L, Martin DM, et al. The motor and tail regions of myosin XV are critical for normal structure and function of auditory and vestibular hair cells. Hum Mol Genet. 2000 Jul 22;9(12):1729-1738. doi: 10.1093/hmg/9.12.1729
  12. Belyantseva IA, Boger ET, Friedman TB. Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13958-13963. doi: 10.1073/ pnas. 2334417100
  13. Wang A, Liang Y, Fridell RA, Probst FJ, Wilcox ER, Touchman JW, et al. Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. Science. 1998 May 29; 280(5368): 1447-1451. doi: 10.1126/ science.280.5368.1447
  14. Wang L, Zhang Y, Xue Q, Huang P, Liu X. Identification of novel compound heterozygous mutations of the MYO15A gene with autosomal recessive non-syndromic hearing loss. J Clin Lab Anal. 2022 Oct;36(10):e24653. doi: 10.1002/jcla. 24653
  15. Cengiz FB, Duman D, Sirmaci A, Tokgöz-Yilmaz S, Erbek S, Oztürkmen-Akay H, et al. Recurrent and private MYO15A mutations are associated with deafness in the Turkish population. Genet Test Mol Biomarkers. 2010 Aug;14(4):543-550. doi: 10.1089/ gtmb. 2010.0039
  16. 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 Feb;55(2):99-102. doi: 10.1016/j.ejmg. 2011. 12.003
  17. Zhang F, Xu L, Xiao Y, Li J, Bai X, Wang H. Three MYO15A Mutations Identified in One Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss. Neural Plast. 2018 Apr 5;2018:5898025. doi: 10.1155/2018/5898025
  18. 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(2):587–96. doi: 10.2298/ GENSR1602587A
  19. Del Castillo I, Morín M, Domínguez-Ruiz M, Moreno-Pelayo MA. Genetic etiology of non-syndromic hearing loss in Europe. Hum Genet. 2022 Apr;141(3-4):683-696. doi: 10.1007/s00439-021-02425-6
  20. Vona B, Doll J, Hofrichter MAH, Haaf T. Nonsyndromic hearing loss: Clinical and diagnostic challenges. Med Genet. 2020;32(2):117-129. doi: 10.1515/medgen-2020-2022
  21. Farjami M, Assadi R, Afzal Javan F, Alimardani M, Eslami S, Mansoori Derakhshan S, et al. The worldwide frequency of MYO15A gene mutations in patients with non-syndromic hearing loss: A meta-analysis. Iran J Basic Med Sci. 2020 Jul;23(7):841-848. doi: 10.22038/ IJBMS. 2020.35977.8563
  22. Elsayed O, Al-Shamsi A. Mutation spectrum of non-syndromic hearing loss in the UAE, a retrospective cohort study and literature review. Mol Genet Genomic Med. 2022 Nov;10(11):e2052. doi: 10.1002/mgg3.2052
  23. Adadey SM, Wonkam-Tingang E, Twumasi Aboagye E, Nayo-Gyan DW, Boatemaa Ansong M, Quaye O, et al. Connexin Genes Variants Associated with Non-Syndromic Hearing Impairment: A Systematic Review of the Global Burden. Life (Basel). 2020 Oct 28;10(11):258. doi: 10.3390/ life10110258