Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy.
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.
Bénit
Paule
P
INSERM U393, Hôpital Necker-Enfants Malades, Paris, France.
Beugnot
Réjane
R
Chretien
Dominique
D
Giurgea
Irina
I
De Lonlay-Debeney
Pascale
P
Issartel
Jean-Paul
JP
Corral-Debrinski
Marisol
M
Kerscher
Stefan
S
Rustin
Pierre
P
Rötig
Agnès
A
Munnich
Arnold
A
D017668:Age of Onset; D000595:Amino Acid Sequence; D001483:Base Sequence; D001927:Brain Diseases / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D003241:Consanguinity; D004579:Electron Transport / Q000235:genetics; D042967:Electron Transport Complex I; D017809:Fatal Outcome; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics
D021122:Protein Subunits; D022821:RNA Splice Sites; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I