A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I

Am J Hum Genet. 1992 Sep;51(3):457-68.


The molecular lesions in two patients exhibiting classical clinical manifestations of MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome have been investigated. A recently reported disease-related A----G base substitution at nt 3243 of the mtDNA, in the DHU loop of tRNA(Leu), was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA of one patient but was not observed, by either restriction-enzyme analysis or nucleotide sequencing, in the other. To define the molecular lesion in the patient who does not have the A----G base substitution at nt 3243, the total mitochondrial genome of the patient has been sequenced. An A----G base substitution at nt 11084, leading to a Thr-to-Ala amino acid replacement in the ND4 subunit of the respiratory complex I, is suggested to be a disease-related mutation.

Publication types

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

MeSH terms

  • Acidosis, Lactic / enzymology
  • Acidosis, Lactic / genetics
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Brain Diseases / enzymology
  • Brain Diseases / genetics*
  • Cerebrovascular Disorders / enzymology
  • Cerebrovascular Disorders / genetics
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV
  • Female
  • Humans
  • Mitochondria / enzymology*
  • Molecular Sequence Data
  • Mutation / genetics
  • NAD(P)H Dehydrogenase (Quinone) / chemistry
  • NAD(P)H Dehydrogenase (Quinone) / deficiency
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • Polymerase Chain Reaction
  • RNA, Transfer, Leu / genetics*
  • Restriction Mapping
  • Syndrome


  • DNA, Mitochondrial
  • RNA, Transfer, Leu
  • NAD(P)H Dehydrogenase (Quinone)
  • Electron Transport Complex IV