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Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy
Author(s) -
Bénit Paule,
Beugnot Réjane,
Chretien Dominique,
Giurgea Irina,
De LonlayDebeney Pascale,
Issartel JeanPaul,
CorralDebrinski Marisol,
Kerscher Stefan,
Rustin Pierre,
Rötig Agnès,
Munnich Arnold
Publication year - 2003
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10225
Subject(s) - biology , mutation , exon , genetics , intron , hypotonia , mitochondrial dna , hypertrophic cardiomyopathy , gene , compound heterozygosity , respiratory chain , mutant , mitochondrial respiratory chain , microbiology and biotechnology , mitochondrion , biochemistry
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. Hum Mutat 21:582–586, 2003. © 2003 Wiley‐Liss, Inc.