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. 2022 Apr;191(2):865-876.
doi: 10.1007/s11845-021-02656-6. Epub 2021 May 29.

Mutational analysis of mitochondrial tRNA genes in 138 patients with Leber's hereditary optic neuropathy

Jie Shuai  1 , Jian Shi  1 , Ya Liang  2 , Fangfang Ji  2 , Luo Gu  3 , Zhilan Yuan  4
Affiliations

Mutational analysis of mitochondrial tRNA genes in 138 patients with Leber's hereditary optic neuropathy

Jie Shuai et al. Ir J Med Sci. 2022 Apr.

Abstract

Introduction: Mutations in mitochondrial DNA (mtDNA) are the most important causes for Leber's hereditary optic neuropathy (LHON). Of these, three primary mtDNA mutations account for more than 90% cases of this disease. However, to date, little is known regarding the relationship between mitochondrial tRNA (mt-tRNA) variants and LHON.

Aim: In this study, we aimed to investigate the association between mt-tRNA variants and LHON.

Methodology: One hundred thirty-eight LHON patients lacking three primary mutations (ND1 3460G > A, ND4 11778Gxs > A, and ND6 14484 T > C), as well as 266 controls were enrolled in this study. PCR-Sanger sequencing was performed to screen the mt-tRNA variants. Moreover, the phylogenetic analysis, pathogenicity scoring system, as well as mitochondrial functions were performed.

Results: We identified 8 possible pathogenic variants: tRNAPhe 593 T > C, tRNALeu(UUR) 3275C > T, tRNAGln 4363 T > C, tRNAMet 4435A > G, tRNAAla 5587 T > C, tRNAGlu 14693A > G, tRNAThr 15927G > A, and 15951A > G, which may change the structural and functional impact on the corresponding tRNAs, and subsequently lead to a failure in tRNA metabolism. Furthermore, significant reductions in mitochondrial ATP and MMP levels and an overproduction of ROS were observed in cybrid cells containing these mt-tRNA variants, suggesting that these variants may lead to mitochondrial dysfunction which was responsible for LHON.

Conclusion: Our study indicated that mt-tRNA variants were associated with LHON, and screening for mt-tRNA variants were recommended for early detection, diagnosis, and prevention of maternally inherited LHON.

Keywords: LHON; Mitochondrial dysfunction; Mt-tRNA; Pathogenic; Variants.

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References

    1. Yu-Wai-Man P, Griffiths PG, Hudson G et al (2009) Inherited mitochondrial optic neuropathies. J Med Genet 46(3):145–158 - PubMed
    1. Rasool N, Lessell S, Cestari DM (2016) Leber hereditary optic neuropathy: Bringing the lab to the clinic. Semin Ophthalmol 31(1–2):107–116 - PubMed
    1. Yu-Wai-Man P, Griffiths PG, Brown DT et al (2003) The epidemiology of Leber hereditary optic neuropathy in the North East of England. Am J Hum Genet 72(2):333–339 - PubMed
    1. Newman NJ (2005) Hereditary optic neuropathies: from the mitochondria to the optic nerve. Am J Ophthalmol 140(3):517–523 - PubMed
    1. Carelli V, La Morgia C, Valentino ML et al (2009) Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders. Biochim Biophys Acta 1787(5):518–528 - PubMed

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