Is Mitochondrial tRNA phe Variant m.593T.C a Synergistically Pathogenic Mutation in Chinese LHON Families with m.11778G.A?
BibTeX
@MISC{Zhang_ismitochondrial,
author = {A-mei Zhang and Hans-jürgen B and Xiaoyun Jia and Wen Zhang and Shiqiang Li and An Yu and Xin-ying Zhuang and Qingjiong Zhang and Yong-gang Yao},
title = {Is Mitochondrial tRNA phe Variant m.593T.C a Synergistically Pathogenic Mutation in Chinese LHON Families with m.11778G.A?},
year = {}
}
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Abstract
Mitochondrial transfer RNA (mt-tRNA) mutations have been reported to be associated with a variety of diseases. In a previous paper that studied the mtDNA background effect on clinical expression of Leber’s hereditary optic neuropathy (LHON) in 182 Chinese families with m.11778G.A, we found a strikingly high frequency (7/182) of m.593T.C in the mitochondrially encoded tRNA phenylalanine (MT-TF) gene in unrelated LHON patients. To determine the potential role of m.593T.C in LHON, we compared the frequency of this variant in 479 LHON patients with m.11778G.A, 843 patients with clinical features of LHON but without the three known primary mutations, and 2374 Han Chinese from the general populations. The frequency of m.593T.C was higher in LHON patients (14/479) than in suspected LHON subjects (12/843) or in general controls (49/2374), but the difference was not statistically significant. The overall penetrance of LHON in families with both m.11778G.A and m.593T.C (44.6%) was also substantially higher than that of families with only m.11778G.A (32.9%) (P = 0.083). Secondary structure prediction of the MT-TF gene with the wild type or m.593T.C showed that this nucleotide change decreases the free energy. Electrophoretic mobility of the MT-TF genes with the wild type or m.593T.C transcribed in vitro further confirmed the change of secondary structure in the presence of this variant. Although our results could suggest a modest synergistic effect of variant m.593T.C on the LHON causing mutation m.11778G.A, the lack of statistical significance probably due to the relatively small sample size analyzed, makes necessary more studies to
Keyphrases
chinese lhon family mitochondrial trna phe variant synergistically pathogenic mutation wild type lhon patient mt-tf gene statistical significance mitochondrial transfer rna modest synergistic effect trna phenylalanine secondary structure prediction previous paper mtdna background effect high frequency general control suspected lhon subject leber hereditary optic neuropathy nucleotide change unrelated lhon patient clinical feature general population overall penetrance chinese family potential role primary mutation clinical expression secondary structure electrophoretic mobility han chinese free energy small sample size
