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Whole exome sequencing identifies novel compound heterozygous pathogenic variants in the MYO15A gene leading to autosomal recessive non-syndromic hearing loss

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Abstract

Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous disease, for which more than 70 genes have been identified. MYO15A mutations have been reported to cause congenital severe-to-profound HL. In this study, we applied the whole exome sequencing (WES) to find the cause of HL in an Iranian family. A proband from an Iranian non-consanguineous family with hearing impaired parents, was examined via WES, after excluding GJB2 mutations as the most common ARNSHL gene via Sanger sequencing. Co-segregation analysis of the candidate variant was done in the family members. Interpretation of variants was according to the American College of Medical Genetics and Genomics (ACMG) guidelines. WES results showed novel compound heterozygous variants (p.Arg1507Ter and p.Val2815Valfs*10) in the MYO15A gene. These two variants, residing in highly conserved regions, were found to be co-segregating in the family and fulfill the criteria of being categorized as pathogenic, according to the ACMG guidelines. Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL in a patient with ARNSHL, as an example of an extremely heterogeneous disease. In agreement with previous studies, MYO15A is regarded to be important in causing HL in Iran.

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Data availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

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Acknowledgements

We take this opportunity to express our special thanks to the staff at the Isfahan Cochlear Implantation Center and also to the patient and family.

Funding

This work was financially supported by Isfahan University of Medical Sciences Grant Nos. 295176, 396133 and 394805.

Author information

Author notes

  1. Akram Sarmadi, and Samane Nasrniya contributed equally to the study.

Authors and Affiliations

  1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Akram Sarmadi, Samane Nasrniya & Mohammad Amin Tabatabaiefar

  2. Genetics Department, Erythron Pathobiology and Genetics lab, Isfahan, Iran

    Akram Sarmadi, Sina Narrei & Zahra Nouri

  3. Department of Otolaryngology, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

    Hamidreza Abtahi

  4. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran

    Mohammad Amin Tabatabaiefar

  5. GenTArget Corp (GTAC), Deputy of Research and Technology, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohammad Amin Tabatabaiefar

Authors
  1. Akram Sarmadi
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  2. Samane Nasrniya
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  3. Sina Narrei
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  4. Zahra Nouri
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  5. Hamidreza Abtahi
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  6. Mohammad Amin Tabatabaiefar
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Contributions

Study design: MAT; Enrolling patient and clinical data collection: HA; Data collection, analysis, and interpretation: MAT, AS, SN1, SN2 and ZN; manuscript preparation: AS, SN1, ZN; critically reviewed by MAT. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Mohammad Amin Tabatabaiefar.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The study was approved by the Review Board of Isfahan University of Medical Sciences (Grant nos. 295176, 396133 and 394805).

Informed consent

Written informed consent was obtained from all of the participants in the study and a written consent to participate was obtained from the parents of the patient (younger than the age of 16). Written informed consent for publication of clinical details and clinical images was obtained from the all of the participants and from the parents the participant under the age of 18.

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Sarmadi, A., Nasrniya, S., Narrei, S. et al. Whole exome sequencing identifies novel compound heterozygous pathogenic variants in the MYO15A gene leading to autosomal recessive non-syndromic hearing loss. Mol Biol Rep 47, 5355–5364 (2020). https://doi.org/10.1007/s11033-020-05618-w

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