Novel mutations in the TK2 gene associated with fatal mitochondrial DNA depletion myopathy.
Mitochondrial DNA depletion syndromes are a heterogeneous group of childhood neurological disorders characterised by a quantitative abnormality of mitochondrial DNA. We describe two siblings who presented at 8 months and 14 months with myopathy, which rapidly progressed and resulted in death by respiratory failure at age 14 and 18 months, respectively. Muscle biopsy revealed marked respiratory chain defects, with real-time PCR confirming a dramatic depletion of mitochondrial DNA. Sequencing of the thymidine kinase 2 (TK2) gene revealed two, novel heterozygous mutations (p.Q87X and p.N100S) with parental DNA analysis confirming the transmission of mutated alleles.
Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK.
Emma
E
Blakely
Langping
L
He
Julie L
JL
Gardner
Gavin
G
Hudson
John
J
Walter
Imelda
I
Hughes
Douglass M
DM
Turnbull
Robert W
RW
Taylor
D001216:Asparagine / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005192:Family Health; D005260:Female; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D012694:Serine / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*
D004272:DNA, Mitochondrial; D009097:Multienzyme Complexes; D005973:Glutamine; D012694:Serine; D001216:Asparagine; C105339:thymidine kinase 2; D013937:Thymidine Kinase