Mitochondrial tRNAAla 5601C> T variant may affect the clinical expression of the LHON ‑related ND4 11778G> A mutation in a family.

Mitochondrial tRNAAla 5601C>T variant may affect the clinical expression of the LHON‑related ND4 11778G>A mutation in a family. Mol Med Rep. 2019 Nov 22;: Authors: Ding Y, Ye YF, Li MY, Xia BH, Leng JH Abstract Certain mutations in mitochondrial DNA (mtDNA) are associated with Leber's hereditary optic neuropathy (LHON). In particular, the well‑known NADH dehydrogenase 4 (ND4) m.11778G>A mutation is one of the most common LHON‑associated primary mutations worldwide. However, how specific mtDNA mutations, or variants, affect LHON penetrance is not fully understood. The aim of the current study was to explore the relationship between mtDNA mutations and LHON, and to provide useful information for early detection and prevention of this disease. Following the molecular characterization of a Han Chinese family with maternally inherited LHON, four out of eight matrilineal relatives demonstrated varying degrees of both visual impairment and age of onset. Through PCR amplification of mitochondrial genomes and direct Sanger sequencing analysis, a homoplasmic mitochondrial‑encoded ND4 m.11778G>A mutation, alongside a set of genetic variations belonging to human mtDNA haplogroup B5b1 were identified. Among these sequence variants, alanine transfer RNA (tRNA)Ala m.5601C>T was of particular interest. This variant occurred at position 59 in the TψC loop and altered the base pairing, which led to mitochondrial RNA (mt‑RNA) metabolism failure ...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research

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