Document Detail

Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion.
MedLine Citation:
PMID:  20083405     Owner:  NLM     Status:  MEDLINE    
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.
Nicole Lesko; Karin Naess; Rolf Wibom; Nicola Solaroli; Inger Nennesmo; Ulrika von D?beln; Anna Karlsson; Nils-G?ran Larsson
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-18
Journal Detail:
Title:  Neuromuscular disorders : NMD     Volume:  20     ISSN:  1873-2364     ISO Abbreviation:  Neuromuscul. Disord.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-17     Completed Date:  2010-06-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111470     Medline TA:  Neuromuscul Disord     Country:  England    
Other Details:
Languages:  eng     Pagination:  198-203     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier B.V. All rights reserved.
Department of Laboratory Medicine, Division of Metabolic Diseases, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Adenosine Triphosphate / metabolism
Arginine / genetics
Child, Preschool
DNA Mutational Analysis / methods
DNA, Mitochondrial / genetics*
Genetic Predisposition to Disease*
Infant, Newborn
Mitochondria / metabolism
Mitochondria, Muscle / genetics,  metabolism
Mitochondrial Diseases / mortality
Mitochondrial Encephalomyopathies / genetics*,  pathology
Muscle, Skeletal / metabolism,  pathology
Mutagenesis, Site-Directed / methods
Mutation / genetics*
Thymidine Kinase / genetics*
Tryptophan / genetics
Reg. No./Substance:
0/DNA, Mitochondrial; 56-65-5/Adenosine Triphosphate; 73-22-3/Tryptophan; 74-79-3/Arginine; EC 2.7.1.-/thymidine kinase 2; EC Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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