A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis

Hum Genet. 2003 Jul;113(2):118-22. doi: 10.1007/s00439-003-0946-0. Epub 2003 Apr 23.


Mitochondrial respiratory chain complex III (ubiquinol-cytochrome c reductase) consists of 11 subunits, only one (cytochrome b) being encoded by the mitochondrial DNA. Disorders of complex III are comparatively rare but are nevertheless present as a clinically heterogeneous group of diseases. To date, no mutation in any of the nuclear-encoded subunits has been described. We report here a deletion in the nuclear gene UQCRB encoding the human ubiquinone-binding protein of complex III (QP-C subunit or subunit VII) in a consanguineous family with an isolated complex III defect. In the proband, a homozygous 4-bp deletion was identified at nucleotides 338-341 of the cDNA predicting both a change in the last seven amino acids and an addition of a stretch of 14 amino acids at the C-terminal end of the protein. Both parents were found to be heterozygous for the deletion, which was absent from 55 controls. Low temperature (-196 degrees C) spectral studies performed on isolated mitochondria from cultured skin fibroblast of the proband showed a decreased cytochrome b content suggestive of a role for the QP-C subunit in the assembly or maintenance of complex III structure.

Publication types

  • Case Reports

MeSH terms

  • Acidosis, Lactic / genetics*
  • Acidosis, Lactic / metabolism
  • Amino Acid Sequence
  • Carrier Proteins / genetics*
  • Cold Temperature
  • Cytochrome b Group / analysis
  • Electron Transport Complex III / deficiency*
  • Female
  • Fibroblasts / enzymology
  • Gene Deletion*
  • Hepatocytes / enzymology
  • Humans
  • Hypoglycemia / genetics*
  • Hypoglycemia / metabolism
  • Infant
  • Lymphocytes / enzymology
  • Mitochondria / enzymology
  • Molecular Sequence Data
  • Skin / pathology


  • Carrier Proteins
  • Cytochrome b Group
  • ubiquinone-binding proteins
  • Electron Transport Complex III