Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit

Am J Hum Genet. 1998 Feb;62(2):262-8. doi: 10.1086/301716.


We report the cDNA cloning, chromosomal localization, and a mutation in the human nuclear gene encoding the 18-kD (AQDQ) subunit of the mitochondrial respiratory chain complex I. The cDNA has an open reading frame of 175 amino acids and codes for a protein with a molecular mass of 23.2 kD. Its gene was mapped to chromosome 5. A homozygous 5-bp duplication, destroying a consensus phosphorylation site, in the 18-kD cDNA was found in a complex I-deficient patient. The patient showed normal muscle morphology and a remarkably nonspecific fatal progressive phenotype without increased lactate concentrations in body fluids. The child's parents were heterozygous for the mutation. In 19 other complex I-deficient patients, no mutations were found in the 18-kD gene.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 5*
  • Fatal Outcome
  • Female
  • Genetic Carrier Screening
  • Humans
  • Infant
  • Lactates / analysis
  • Male
  • Metabolism, Inborn Errors / enzymology
  • Metabolism, Inborn Errors / genetics*
  • Mitochondria, Muscle / enzymology
  • Mitochondria, Muscle / pathology
  • Molecular Sequence Data
  • Muscle, Skeletal / pathology
  • NAD(P)H Dehydrogenase (Quinone) / chemistry
  • NAD(P)H Dehydrogenase (Quinone) / deficiency*
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • Nuclear Family
  • Repetitive Sequences, Nucleic Acid*


  • Lactates
  • NAD(P)H Dehydrogenase (Quinone)