Mutational analysis of mitochondrial tRNA genes in 138 patients with Leber's hereditary optic neuropathy.
Ir J Med Sci
; 191(2): 865-876, 2022 Apr.
Article
em En
| MEDLINE
| ID: mdl-34053002
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Atrofia Óptica Hereditária de Leber
Tipo de estudo:
Prognostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Ir J Med Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China