@article{2996125,
    title = "New mutations in TK2 gene associated with mitochondrial DNA depletion",
    author = "Galbiati, S. and Bordoni, A. and Papadimitriou, D. and Toscano, A. and Rodolico, C. and Katsarou, E. and Sciacco, M. and Garufi, A. and Prelle, A. and Aguennouz, M. and Bonsignore, M. and Crimi, M. and Martinuzzi, A. and Bresolin, N. and Papadimitriou, A. and Comi, G.P.",
    journal = "Pediatric Neurology",
    year = "2006",
    volume = "34",
    number = "3",
    pages = "177-185",
    issn = "0887-8994",
    doi = "10.1016/j.pediatrneurol.2005.07.013",
    keywords = "adenosine diphosphate;  alanine;  cysteine;  leucine;  long chain fatty acid coenzyme A ligase;  mitochondrial DNA;  nucleic acid;  proline;  thymidine kinase;  tryptophan;  valine, article;  case report;  chemical analysis;  child;  clinical feature;  disease course;  dystrophy;  encephalomyopathy;  family;  gene mutation;  homozygosity;  human;  human tissue;  male;  mitochondrial DNA depletion;  muscle biopsy;  muscle mitochondrion;  myopathy;  neurologic examination;  nuclear magnetic resonance imaging;  nucleotide sequence;  priority journal;  psychomotor development;  seizure, Amino Acid Substitution;  Biopsy;  Child;  Child, Preschool;  Chromosome Aberrations;  Diagnosis, Differential;  Disease Progression;  DNA Mutational Analysis;  DNA, Mitochondrial;  Electron Transport Complex IV;  Epilepsy;  Female;  Genes, Recessive;  Genotype;  Heterozygote Detection;  Homozygote;  Humans;  Infant;  Male;  Mitochondrial Encephalomyopathies;  Muscle, Skeletal;  Phenotype;  Psychomotor Disorders;  Thymidine Kinase",
    abstract = "Mitochondrial deoxyribonucleic acid depletion syndromes are autosomal recessive disorders characterized by a reduction of the amount of mitochondrial deoxyribonucleic acid, which impairs the synthesis of respiratory chain complexes. Mutations in the deoxyguanosine kinase and polymerase γ genes have been identified in hepatocerebral forms, whereas thymidine kinase 2 gene mutations have been found in patients with isolated myopathy, encephalomyopathy, or spinal muscular atrophy. Mutations in the gene encoding the β subunit of the adenosine diphosphate-forming succinyl-coenzyme A synthetase have also been reported in a family. In this report, the clinical, molecular, morphologic, and biochemical features of five children from two independent families with an infantile encephalomyopathy are characterized. The affected children manifested muscle mitochondrial deoxyribonucleic acid depletion and three novel thymidine kinase 2 gene mutations. They consist of a homozygous substitution resulting in Ala to Val change at the highly conserved position 181 of thymidine kinase in the first family, and two heterozygous substitutions in the second family: a Cys to Trp change at residue 108 and a Leu to Pro change at residue 257 of the enzyme. Common clinical features associated with these TK2 mutations are a normal early developmental phase followed by psychomotor regression, encephalopathy often with epileptic seizures, and myopathy with features of a progressive dystrophic process. © 2006 by Elsevier Inc. All rights reserved."
}