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Journal Article

Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion

MPS-Authors

Lesko,  Nicole
Max Planck Society;

Naess,  Karin
Max Planck Society;

Wibom,  Rolf
Max Planck Society;

Solaroli,  Nicola
Max Planck Society;

Nennesmo,  Inger
Max Planck Society;

von Döbeln,  Ulrika
Max Planck Society;

Karlsson,  Anna
Max Planck Society;

Larsson,  Nils-Göran
Max Planck Society;

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Citation

Lesko, N., Naess, K., Wibom, R., Solaroli, N., Nennesmo, I., von Döbeln, U., et al. (2010). Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion. Neuromuscul Disord, 20(3), 198-203.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-593E-A
Abstract
Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy. TK2 is a mitochondrial deoxyribonucleoside kinase required for the phosphorylation of deoxycytidine and deoxythymidine and hence is vital for the maintenance of a balanced mitochondrial dNTP pool in post-mitotic tissues. We describe a patient with two novel TK2 mutations, which caused disease onset shortly after birth and death at the age of three months. One mutation (219insCG) generated an early stop codon, thus preventing the synthesis of a functional protein. The second mutation (R130W) resulted in an amino acid substitution, which caused a severe reduction (<3%) of TK2 enzyme activity. These two novel TK2 mutations cause an extremely severe phenotype with overwhelming central nervous system symptoms not commonly seen in patients with TK2-deficiency. We conclude that the severe clinical presentation in this patient was due to a virtual lack of mitochondrial TK2 activity.