Abstract
Mitochondrial diseases are associated with defects of adenosine triphosphate production and energy supply to organs as a result of dysfunctions of the mitochondrial respiratory chain. Biallelic mutations in the YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase cause myopathy, lactic acidosis, and sideroblastic anemia 2 (MLASA2), a type of mitochondrial disease. Here, we report a consanguineous Turkish family with two siblings showing severe metabolic decompensation including recurrent hypoglycemia, lactic acidosis, and transfusion-dependent anemia. Using whole-exome sequencing of the proband and his parents, we identified a novel YARS2 mutation (c.1303A>G, p.Ser435Gly) that was homozygous in the patient and heterozygous in his parents. This mutation is located at the ribosomal protein S4-like domain of the gene, while other reported YARS2 mutations are all within the catalytic domain. Interestingly, the proband showed more severe symptoms and an earlier onset than previously reported patients, suggesting the functional importance of the S4-like domain in tyrosyl-tRNA synthetase.
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Acknowledgements
We thank the patient and his family for participating in this work. We also thank Ms S Sugimoto and K Takabe for technical assistance. This work was supported by research grants from the Ministry of Health, Labour and Welfare (N. Matsumoto, N. Miyake), the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Ministry of Education, Culture, Sports, Science and Technology (N. Matsumoto), the Strategic Research Program for Brain Sciences (N. Matsumoto), a Grant-in-Aid for Scientific Research on Innovative Areas-(Transcription cycle)-from the Ministry of Education, Culture, Sports, Science and Technology of Japan (N. Matsumoto), a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (H. Saitsu, N. Matsumoto, N. Miyake), the Takeda Science Foundation (N. Matsumoto, N. Miyake), and the Hayashi Memorial Foundation for Female Natural Scientists (N. Miyake).
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Nakajima, J., Eminoglu, T., Vatansever, G. et al. A novel homozygous YARS2 mutation causes severe myopathy, lactic acidosis, and sideroblastic anemia 2. J Hum Genet 59, 229–232 (2014). https://doi.org/10.1038/jhg.2013.143
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DOI: https://doi.org/10.1038/jhg.2013.143
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