Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 28:17:77-89.
doi: 10.2147/PGPM.S441281. eCollection 2024.

The Association Between Mitochondrial tRNAGlu Variants and Hearing Loss: A Case-Control Study

Xuejiao Yu  1 , Sheng Li  2 , Qinxian Guo  3 , Jianhang Leng  3 , Yu Ding  3
Affiliations

The Association Between Mitochondrial tRNAGlu Variants and Hearing Loss: A Case-Control Study

Xuejiao Yu et al. Pharmgenomics Pers Med. .

Abstract

Purpose: This study aimed to examine the frequencies of mt-tRNAGlu variants in 180 pediatric patients with non-syndromic hearing loss (NSHL) and 100 controls.

Methods: Sanger sequencing was performed to screen for mt-tRNAGlu variants. These mitochondrial DNA (mtDNA) pathogenic mutations were further assessed using phylogenetic conservation and haplogroup analyses. We also traced the origins of the family history of probands carrying potential pathogenic mtDNA mutations. Mitochondrial functions including mtDNA content, ATP and reactive oxygen species (ROS) were examined in cells derived from patients carrying the mt-tRNAGlu A14692G and CO1/tRNASer(UCN) G7444A variants and controls.

Results: We identified four possible pathogenic variants: m.T14709C, m.A14683G, m.A14692G and m.A14693G, which were found in NSHL patients but not in controls. Genetic counseling suggested that one child with the m.A14692G variant had a family history of NSHL. Sequence analysis of mtDNA suggested the presence of the CO1/tRNASer(UCN) G7444A and mt-tRNAGlu A14692G variants. Molecular analysis suggested that, compared with the controls, patients with these variants exhibited much lower mtDNA copy numbers, ATP production, whereas ROS levels increased (p<0.05 for all), suggesting that the m.A14692G and m.G7444A variants led to mitochondrial dysfunction.

Conclusion: mt-tRNAGlu variants are important risk factors for NSHL.

Keywords: deafness; mitochondrial tRNAGlu variants; pediatrics; tRNA metabolism.

Plain language summary

The main aim of our study was to explore the association between the mt-tRNAGlu variants and hearing loss. We found that m.T14709C, m.A14683G, m.A14692G and m.A14693G variants were associated with hearing impairments, these variants localized at extremely conserved nucleotides of mt-tRNAGlu and may result a failure in tRNA metabolism, furthermore, patients with mt-tRNAGlu variants exhibited much lower levels of mtDNA copy number, ATP as compared with controls, whereas ROS increased. As a result, mt-tRNAGlu variants may serve as biomarkers for mitochondrial deafness, and screening for tRNAGlu variants is recommended for early detection and diagnosis of mitochondrial deafness.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests in this work.

Figures

Figure 1
Figure 1
One Han Chinese family with NSHL, arrow indicated the proband.
Figure 2
Figure 2
PCR amplification of mt-tRNAGlu gene in subjects with NSHL, arrow indicated the PCR product, which was 1050-bp.
Figure 3
Figure 3
Sequence alignment of mt-tRNAGlu gene from different species, arrows indicated the positions of 37, 54, 55 and 64, corresponding to the m.T14709C, m.A14693G, m.A14692G and m.A14683G variants.
Figure 4
Figure 4
Cloverleaf structure of mt-tRNAGlu gene, arrows indicated the positions of m.T14709C, m.A14693G, m.A14692G and m.A14683G variants.
Figure 5
Figure 5
Audiological examination of matrilineal relatives of one pedigree with NSHL, (X) left ear; (O) right ear.
Figure 6
Figure 6
Identification of m.A14692G and m.G7444A variants by direct sequencing analysis.
Figure 7
Figure 7
Location of deafness-associated variants in tRNASer(UCN) and adjacent CO1. Arrow indicated the m.G7444A variant in the precursor of this tRNA and adjacent sequence of CO1 from wild-type (WT) and mutant (MT).
Figure 8
Figure 8
Analysis of mtDNA copy number in matrilineal relatives of the pedigree with NSHL. (A) mtDNA copy number; (B) ATP content; (C) ROS qualifications.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Jafarlou F, Najafi B, Sameni SJ. Is newborn hearing screening cost effective? Economic consideration for policy makers. Int J Prev Med. 2021;12:155. doi:10.4103/ijpvm.IJPVM_270_20 - DOI - PMC - PubMed
    1. Marinelli JP, Lohse CM, Fussell WL, et al. Association between hearing loss and development of dementia using formal behavioural audiometric testing within the Mayo Clinic Study of Aging (MCSA): a prospective population-based study. Lancet Healthy Longev. 2022;3(12):e817–e824. doi:10.1016/S2666-7568(22)00241-0 - DOI - PMC - PubMed
    1. Ding Y, Leng J, Fan F, et al. The role of mitochondrial DNA mutations in hearing loss. Biochem Genet. 2013;51(7–8):588–602. doi:10.1007/s10528-013-9589-6 - DOI - PubMed
    1. Bitner-Glindzicz M. Hereditary deafness and phenotyping in humans. Br Med Bull. 2002;63(1):73–94. doi:10.1093/bmb/63.1.73 - DOI - PubMed
    1. Taylor RW, Turnbull DM. Mitochondrial DNA mutations in human disease. Nat Rev Genet. 2005;6(5):389–402. doi:10.1038/nrg1606 - DOI - PMC - PubMed