LHON/MELAS Overlap Syndrome Associated With a Mitochondrial MTND1 Gene Mutation

Eur J Hum Genet. 2005 May;13(5):623-7. doi: 10.1038/sj.ejhg.5201363.

Abstract

Pathogenic point mutations in the mitochondrial MTND1 gene have previously been described in association with two distinct clinical phenotypes -- Leber hereditary optic neuropathy (LHON) and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Here we report the first heteroplasmic mitochondrial DNA (mtDNA) point mutation (3376G>A) in the MTND1 gene associated with an overlap syndrome comprising the clinical features of both LHON and MELAS. Muscle histochemistry revealed subtle mitochondrial abnormalities, while biochemical analysis showed an isolated complex I deficiency. Our findings serve to highlight the growing importance of mutations in mitochondrial complex I structural genes in MELAS and its associated overlap syndromes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex I / metabolism
  • Female
  • Humans
  • MELAS Syndrome / complications
  • MELAS Syndrome / genetics*
  • MELAS Syndrome / physiopathology
  • NADH Dehydrogenase / genetics*
  • Optic Atrophy, Hereditary, Leber / complications
  • Optic Atrophy, Hereditary, Leber / genetics*
  • Optic Atrophy, Hereditary, Leber / physiopathology
  • Pedigree
  • Point Mutation

Substances

  • DNA, Mitochondrial
  • NADH Dehydrogenase
  • Electron Transport Complex I
  • MT-ND1 protein, human