Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy

Hum Mutat. 2003 Jun;21(6):582-6. doi: 10.1002/humu.10225.


Respiratory chain complex I deficiencies represent a genetically heterogeneous group of diseases resulting from mutations in either mitochondrial or nuclear DNA. Combination of denaturing high performance liquid chromatography and sequence analysis allowed us to show that a 4-bp deletion in intron 2 (IVS2+5_+8delGTAA) of the NDUFV2 gene (encoding NADH dehydrogenase ubiquinone flavoprotein 2) causes complex I deficiency and early onset hypertrophic cardiomyopathy with trunk hypotonia in three affected sibs of a consanguineous family. The homozygous mutation altering the consensus splice-donor site of exon 2 resulted in 70% decreased NDUFV2 protein and complex I deficiency. While mutation in a number of genes encoding complex I subunits essentially result in neurological symptoms, this first mutation in NDUFV2 is strikingly associated with cardiomyopathy, as previously observed in the unique case of NDFUS2 mutations.

Publication types

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

MeSH terms

  • Age of Onset
  • Amino Acid Sequence
  • Base Sequence
  • Brain Diseases / genetics*
  • Cardiomyopathy, Hypertrophic / genetics*
  • Consanguinity
  • Electron Transport / genetics
  • Electron Transport Complex I
  • Fatal Outcome
  • Female
  • Homozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • NADH, NADPH Oxidoreductases / chemistry
  • NADH, NADPH Oxidoreductases / genetics*
  • Protein Subunits / genetics*
  • RNA Splice Sites / genetics


  • Protein Subunits
  • RNA Splice Sites
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex I

Associated data

  • OMIM/600532
  • RefSeq/NM_021074