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Mitochondrial DNA depletion in single fibers in a patient with novel TK2 mutations
Department of Pathology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
Department of Pathology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
Department of Women's and Children's Health, Uppsala University Children's Hospital, Sweden. (Barnneurologisk forskning/Ahlsten)
Department of Pathology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
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2014 (Engelska)Ingår i: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 24, nr 8, s. 713-720Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The mitochondrial DNA (mtDNA) depletion syndrome is a genetically heterogeneous group of diseases caused by nuclear gene mutations and secondary reduction in mtDNA copy number. We describe a patient with progressive muscle weakness and increased creatine kinase and lactate levels. Muscle weakness was first noted at age 1.5 years and he died of respiratory failure and bronchopneumonia at age 3.5 years. The muscle biopsy showed dystrophic features with ragged red fibers and numerous cytochrome c oxidase (COX)-negative fibers. qPCR analysis demonstrated depletion of mtDNA and sequence analysis of the mitochondrial thymidine kinase 2 (TK2) gene revealed two novel heterozygous variants, c.332C > T, p.(T111I) and c.156 + 5G > C. Quantitative analysis of mtDNA in single muscle fibers demonstrated that COX-deficient fibers showed more pronounced depletion of mtDNA when compared with fibers with residual COX activity (P < 0.01, n = 25). There was no evidence of manifestations from other organs than skeletal muscle although there was an apparent reduction of mtDNA copy number also in liver. The patient showed a pronounced, albeit transient, improvement in muscle strength after onset of treatment with coenzyme Q10, asparaginase, and increased energy intake, suggesting that nutritional modulation may be a therapeutic option in myopathic mtDNA depletion syndrome.

Ort, förlag, år, upplaga, sidor
2014. Vol. 24, nr 8, s. 713-720
Nyckelord [en]
Mitochondrial DNA depletion syndrome, Myopathy, Thymidine kinase 2, TK2, Mitochondrial myopathy
Nationell ämneskategori
Neurologi
Identifikatorer
URN: urn:nbn:se:uu:diva-231210DOI: 10.1016/j.nmd.2014.05.009ISI: 000340317200009OAI: oai:DiVA.org:uu-231210DiVA, id: diva2:745115
Forskningsfinansiär
Vetenskapsrådet, 07122
Anmärkning

Christoffer Ehrstedt ingår i forskargruppen Barnneurologisk forskning, institutionen för kvinnors och barns hälsa, Uppsala universitet.

Tillgänglig från: 2014-09-09 Skapad: 2014-09-05 Senast uppdaterad: 2017-12-05Bibliografiskt granskad

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