A defect in the thymidine kinase 2 gene causing isolated mitochondrial myopathy without mtDNA depletion

• Published in: European journal of paediatric neurology 2008-07, Vol.12 (4), p.309-313
• Main Authors: Leshinsky-Silver, E, Michelson, M, Cohen, S, Ginsberg, M, Sadeh, M, Barash, V, Lerman-Sagie, T, Lev, D
• Format: Article
• Language: English
• Subjects: Blotting, Southern; Child; DNA Mutational Analysis - methods; DNA, Mitochondrial - analysis; DNA, Mitochondrial - genetics; DNA, Mitochondrial - isolation & purification; Humans; Male; Microscopy, Electron; Mitochondrial Myopathies - genetics; Mitochondrial Myopathies - pathology; Mitochondrial myopathy; mtDNA depletion; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal - ultrastructure; Neurology; Pediatrics; Polymerase Chain Reaction; Respiratory chain; Thymidine Kinase - genetics; Thymidine kinase 2
• ISSN: 1090-3798; 1532-2130
• DOI: 10.1016/j.ejpn.2007.09.005

Abstract Isolated mitochondrial myopathies (IMM) are either due to primary defects in mtDNA, in nuclear genes that control mtDNA abundance and structure such as thymidine kinase 2 (TK2), or due to CoQ deficiency. Defects in the TK2 gene have been found to be associated with mtDNA depletion attributed to a depleted mitochondrial dNTP pool in non-dividing cells. We report an unusual case of IMM, homozygous for the H90N mutation in the TK2 gene but unlike other cases with the same mutation, does not demonstrate mtDNA depletion. The patient's clinical course is relatively mild and a muscle biopsy showed ragged red muscle fibers with a mild decrease in complexes I and an increase in complexes IV and II activities. This report extends the phenotypic expression of TK2 defects and suggests that all patients who present with an IMM even with normal quantities of mtDNA should be screened for TK2 mutations.