A Lethal Defect of Mitochondrial and Peroxisomal Fission

N Engl J Med. 2007 Apr 26;356(17):1736-41. doi: 10.1056/NEJMoa064436.

Abstract

We report on a newborn girl with microcephaly, abnormal brain development, optic atrophy and hypoplasia, persistent lactic acidemia, and a mildly elevated plasma concentration of very-long-chain fatty acids. We found a defect of the fission of both mitochondria and peroxisomes, as well as a heterozygous, dominant-negative mutation in the dynamin-like protein 1 gene (DLP1). The DLP1 protein has previously been implicated, in vitro, in the fission of both these organelles. Overexpression of the mutant DLP1 in control cells reproduced the fission defect. Our findings are representative of a class of disease characterized by defects in both mitochondria and peroxisomes.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Acidosis, Lactic / genetics
  • Eye Abnormalities / genetics
  • Fatal Outcome
  • Fatty Acids / blood
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Infant, Newborn
  • Male
  • Microcephaly / genetics
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria / metabolism
  • Mitochondria / physiology*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Muscle Hypotonia / genetics
  • Mutation*
  • Open Reading Frames / genetics
  • Peroxisomes / metabolism
  • Peroxisomes / physiology*
  • Sequence Analysis, DNA

Substances

  • Fatty Acids
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • DNM1L protein, human