Is mitochondrial tRNA(phe) variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A?
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...
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2011
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oai:doaj.org-article:6c0fe2eead344157a12c7d53c6b77be52021-11-18T07:36:05ZIs mitochondrial tRNA(phe) variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A?1932-620310.1371/journal.pone.0026511https://doaj.org/article/6c0fe2eead344157a12c7d53c6b77be52011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22039503/?tool=EBIhttps://doaj.org/toc/1932-6203Mitochondrial 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 confirm this effect.A-Mei ZhangHans-Jürgen BandeltXiaoyun JiaWen ZhangShiqiang LiDandan YuDong WangXin-Ying ZhuangQingjiong ZhangYong-Gang YaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26511 (2011) |
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Medicine R Science Q A-Mei Zhang Hans-Jürgen Bandelt Xiaoyun Jia Wen Zhang Shiqiang Li Dandan Yu Dong Wang Xin-Ying Zhuang Qingjiong Zhang Yong-Gang Yao Is mitochondrial tRNA(phe) variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A? |
| description |
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 confirm this effect. |
| format |
article |
| author |
A-Mei Zhang Hans-Jürgen Bandelt Xiaoyun Jia Wen Zhang Shiqiang Li Dandan Yu Dong Wang Xin-Ying Zhuang Qingjiong Zhang Yong-Gang Yao |
| author_facet |
A-Mei Zhang Hans-Jürgen Bandelt Xiaoyun Jia Wen Zhang Shiqiang Li Dandan Yu Dong Wang Xin-Ying Zhuang Qingjiong Zhang Yong-Gang Yao |
| author_sort |
A-Mei Zhang |
| title |
Is mitochondrial tRNA(phe) variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A? |
| title_short |
Is mitochondrial tRNA(phe) variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A? |
| title_full |
Is mitochondrial tRNA(phe) variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A? |
| title_fullStr |
Is mitochondrial tRNA(phe) variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A? |
| title_full_unstemmed |
Is mitochondrial tRNA(phe) variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A? |
| title_sort |
is mitochondrial trna(phe) variant m.593t>c a synergistically pathogenic mutation in chinese lhon families with m.11778g>a? |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/6c0fe2eead344157a12c7d53c6b77be5 |
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