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

✍ Scribed by Paule Bénit; Réjane Beugnot; Dominique Chretien; Irina Giurgea; Pascale De Lonlay-Debeney; Jean-Paul Issartel; Marisol Corral-Debrinski; Stefan Kerscher; Pierre Rustin; Agnès Rötig; Arnold Munnich

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 140 KB
• Volume: 21
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.10225

✦ Synopsis

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.