Neuromuscular disease presentation with three genetic defects involving two genomes
Received 12 August 2009; received in revised form 16 September 2009; accepted 2 October 2009.
Abstract
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 tRNALeu(CUN) (MTTL2) gene mutation.
aMitochondrial Research Group and NCG Rare Mitochondrial Disorders of Adults and Children Service, Newcastle University, Newcastle upon Tyne, UK
bRegional Neurosciences Centre, Newcastle General Hospital, Newcastle upon Tyne, UK
cInstitute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK
Corresponding author. Address: Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Tel.: +44 191 2223685; fax: +44 191 2824373.
ABSTRACT