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Maternally inherited non-syndromic hearing loss is linked with a novel mitochondrial ND6 gene mutation

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Abstract

Background

Maternally inherited non-syndromic hearing loss is linked with mitochondrial DNA mutations.

Aim

This investigation demonstrates the features of a Chinese pedigree suffering from maternally inherited non-syndromic hearing loss.

Methods

Biochemical characterizations included the measurements ofprotein synthesis levels, membrane potential, and the synthesis of reactive oxygen species (ROS) and adenosine triphosphate (ATP) using cybrid cell lines derived from an affected matrilineal subject and control subject.

Results

Non-congenital early or late-onset/development hearing impairment has been observed in 4 of 9 in a family (matrilineal), with different degrees of hearing impairment, ranging from normal to severe. A pedigree’s whole mitochondrial genome sequence analysis revealed the homoplasmic m.14502 T > C (I58V) mutation at ND6’s isoleucine location-58, and specific mitocchondrial DNA polymorphisms set haplogroups M10 were highly conserved. In vitro models indicated that m.14502 T > C mutation-derived respiratory deficiency decreases ND6 protein synthesis, mitochondrial membrane potential, and ATP synthesis. These mitochondrial dysregulations enhance the generation of ROS in the mutant cells. Identifying nuclear modifiers is essential for elucidating hearing loss’s pathogenesis and furnishing novel therapeutic interventions.

Conclusions

The m.14502 T > C mutation should be considered an inherited risk factor that can help diagnose. The data of this investigation help counsel families of individuals with hearing loss.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Funding

This study was funded by the Scientific Research fund of Taizhou Science and Technology Bureau (NO. 20ywb135) and Wenling Science and Technology Project (NO.2020S0180128; 2019S0180051; 2021S00152).

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, The Affiliated Wenling Hospital, Wenzhou Medical University, Wenling, 317500, Zhejiang, China

    Ting Zhang

  2. ENT Department, The First People’s Hospital of Wenling, Taizhou University, Taizhou, China

    Renjie Su, Wen Xiang & Wenbin Wang

  3. ENT Department, The Affiliated Wenling Hospital of Wenzhou Medical University, Taizhou, China

    Renjie Su, Wen Xiang & Wenbin Wang

  4. The First People’s Hospital of Wenling, Taizhou University, 333 Chuanannan Road, Taizhou, 317500, China

    Wenbin Wang

Authors
  1. Ting Zhang
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  2. Renjie Su
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  3. Wen Xiang
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  4. Wenbin Wang
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Contributions

Ting Zhang and Wenbin Wang designed the study. Ting Zhang, Renjie Su, and Wen Xiang acquired the data. Wenbin Wang wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

Corresponding author

Correspondence to Wenbin Wang.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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All authors declare no competing interests.

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Zhang, T., Su, R., Xiang, W. et al. Maternally inherited non-syndromic hearing loss is linked with a novel mitochondrial ND6 gene mutation. Ir J Med Sci 193, 937–943 (2024). https://doi.org/10.1007/s11845-023-03484-6

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  • DOI: https://doi.org/10.1007/s11845-023-03484-6

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