Neuromuscular disease presentation with three genetic defects involving two genomes.
An extensive range of molecular defects have been identified in the human mitochondrial genome (mtDNA), many associated with well-characterised, progressive neurological syndromes. We describe a patient who presented to a mitochondrial clinic with progressive bilateral ptosis, external opthalmoplegia and increasing difficulty with walking. He had previously been diagnosed with a dominant, demyelinating polyneuropathy due to PMP22 gene duplication and had also developed gout, presenting in acute renal failure, due to an X-linked recessive HPRT gene mutation. Muscle biopsy revealed many COX-deficient fibres which we show contain high levels of a third genetic defect--a novel, mitochondrial tRNA(Leu(CUN)) (MTTL2) gene mutation.
Mitochondrial Research Group and NCG Rare Mitochondrial Disorders of Adults and Children Service, Newcastle University, Newcastle upon Tyne, UK.
Mazhor
M
Al-Dosary
Roger G
RG
Whittaker
Joanna
J
Haughton
Robert
R
McFarland
Judith
J
Goodship
Douglass M
DM
Turnbull
Robert W
RW
Taylor
D000328:Adult; D003576:Electron Transport Complex IV / Q000378:metabolism; D020440:Gene Duplication; D050172:Genes, X-Linked; D015894:Genome, Human; D054629:Genome, Mitochondrial; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics*; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics*
D009185:Myelin Proteins; C073687:PMP22 protein, human; D012346:RNA, Transfer, Amino Acyl; D003576:Electron Transport Complex IV; D007041:Hypoxanthine Phosphoribosyltransferase