title: Progressive myofiber loss with extensive fibro-fatty replacement in a child with mitochondrial DNA depletion syndrome and novel thymidine kinase 2 gene mutations.
abstract: The mitochondrial DNA depletion syndromes (MDS) are autosomal recessive disorders with a decreased mitochondrial DNA copy number. Mutations in thymidine kinase 2 (TK2) have been responsible for the myopathic form of MDS. We describe a child with congenital muscle weakness who had a progressive mitochondrial myopathy associated with extensive fibro-fatty replacement of myofibers resembling muscular dystrophy. MDS was suspected based upon findings in the initial muscle biopsy. Sequence analysis of the TK2 gene revealed two novel heterozygous mutations: the frame shift mutation, c.255_c.258delAGAA, and the heterozygous missense mutation, c.515G>A, (p.R172Q). This report extends the phenotype and genotype of TK2 defects.
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3026, USA.
authors.forename: James
authors.initials: J
authors.lastname: Collins
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Bove
authors.forename: David
authors.initials: D
authors.lastname: Dimmock
authors.forename: Paula
authors.initials: P
authors.lastname: Morehart
authors.forename: Lee-Jun
authors.initials: LJ
authors.lastname: Wong
authors.forename: Brenda
authors.initials: B
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000473:pathology*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; C105339:thymidine kinase 2; D013937:Thymidine Kinase