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Mitochondrial myopathy due to thymidine kinase 2 deficiency (TK2). Diagnosis and the results of selective screening
https://doi.org/10.25557/2073-7998.2024.06.29-34
Abstract
Mitochondrial myopathy caused by thymidine kinase 2 (TK2) deficiency is an inherited monogenic disease that is part of a group of mitochondrial DNA (mtDNA) maintenance and replication syndromes. These diseases mainly manifest as severe multisystem childhood forms and are characterized by a significant reduction in mtDNA copies in the affected cells and tissues. In Russia, the first cases of TK2- associated myopathy were identified in 2019. The importance of early diagnosis of the disease is due to the emergence of new treatment methods. Aim of the study: to conduct selective screening for TK2 deficiency among 150 patients with a previously excluded diagnosis of spinal muscular atrophy, as well as 50 patients with a presumptive diagnosis of congenital myopathy with a negative test result using panel sequencing. Method: high-throughput sequencing using a panel of mitochondrial disease genes. Results: One heterozygous carrier of a pathogenic variant in the TK2 gene was identified. Additional analysis of Russian exome sequencing databases Ruexac, Ru-seq browser showed an estimated frequency of TK2 deficiency equal to 1:563900, confidence intervals CI (95%) – 218,894:1,454,451.
Supporting agencies: The study was carried out according to the state assignment of the Ministry of Science and Higher Education of the Russian Federation for the RCMG.
About the Authors
P. G. Tsygankova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115522
D. V. Kistol
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115522
P. A. Chausova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115522
E. Y. Zakharova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115522
References
1. Hirano M., Marti R., Ferreiro-Barros C., et al. Defects of intergenomic communication: autosomal disorders that cause multiple deletions and depletion of mitochondrial DNA. Semin Cell Dev Biol. 2001;12(6):417-27.
2. Bourdon A., Minai L., Serre V., et al. Mutation of RRM2B, en- coding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet. 2007;39(6):776-80.
3. Mandel H., Szargel R., Labay V., et al. The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat Genet. 2001;29(3):337-41.
4. Nishino I., Spinazzola A., Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science. 1999;283(5402):689-92.
5. Saada A., Shaag A., Mandel H., Nevo Y., Eriksson S., Elpeleg O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet. 2001;29(3):342-4.
6. Курбатов С.А., Цыганкова П.Г., Моллаева К.Ю. и др. Младенческая и детская форма митохондриальной миопатии с мутациями в гене ТК2 с фенотипом спинальной мышечной атрофии 5q: первые случаи в России. Нервно-мышечные болезни. 2019;9(3):6776. https://doi.org/10.17650/2222-8721-2019-9-3-57-76
7. Рыжкова О.П., Кардымон О.Л., Прохорчук Е.Б. и др. Руководство по интерпретации данных последовательности ДНК человека, полученных методами массового параллельного секвенирования (MPS) (редакция 2018, версия 2). Медицинская генетика 2019; 18(2): 3-23 DOI: 10.25557/20737998.2019.02.3-23.
8. Guo M. H., Gregg, A. R. Estimating yields of prenatal carrier screening and implications for design of expanded carrier screening panels. Genetics in medicine : official journal of the American College of Medical Genetics. 2019; 21(9): 1940–1947.
9. Domínguez-González C., Hernández-Laín A., Rivas E., et al. Late-onset thymidine kinase 2 deficiency: a review of 18 cases. Orphanet J Rare Dis. 2019 May 6;14(1):100. doi: 10.1186/s13023-0191071-z.
10. Garone C., Taylor R.W., Nascimento A., et al. Retrospective natural history of thymidine kinase 2 deficiency. J Med Genet. 2018;55(8):515-21.
11. Mancuso M.., Salviati L, Sacconi S., et al. Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA. Neurology. 2002 Oct 22;59(8):1197-202. doi: 10.1212/01. wnl.0000028689.93049.9a.
12. Bychkov I.O., Itkis Y.S., Tsygankova P.G., et al. Mitochondrial DNA maintenance disorders in 102 patients from different parts of Russia: Mutational spectrum and phenotypes. Mitochondrion. 2021 Mar;57:205-212. doi: 10.1016/j.mito.2021.01.004.
Review
For citations:
Tsygankova P.G., Kistol D.V., Chausova P.A., Zakharova E.Y. Mitochondrial myopathy due to thymidine kinase 2 deficiency (TK2). Diagnosis and the results of selective screening. Medical Genetics. 2024;23(6):29-34. (In Russ.) https://doi.org/10.25557/2073-7998.2024.06.29-34
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