title: Mutations in the complex I NDUFS2 gene of patients with cardiomyopathy and encephalomyopathy.
abstract: Human complex I is built up and regulated by genes encoded by the mitochondrial DNA (mtDNA) as well as the nuclear DNA (nDNA). In recent years, attention mainly focused on the relation between complex I deficiency and mtDNA mutations. However, a high percentage of consanguinity and an autosomal-recessive mode of inheritance observed within our patient group as well as the absence of common mtDNA mutations make a nuclear genetic cause likely. The NDUFS2 protein is part of complex I of many pro- and eukaryotes. The nuclear gene coding for this protein is therefore an important candidate for mutational detection studies in enzymatic complex I deficient patients. Screening of patient NDUFS2 cDNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in combination with direct DNA sequencing revealed three missense mutations resulting in the substitution of conserved amino acids in three families.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Loeffen
authors.forename: O
authors.initials: O
authors.lastname: Elpeleg
authors.forename: J
authors.initials: J
authors.lastname: Smeitink
authors.forename: R
authors.initials: R
authors.lastname: Smeets
authors.forename: S
authors.initials: S
authors.lastname: Stöckler-Ipsiroglu
authors.forename: H
authors.initials: H
authors.lastname: Mandel
authors.forename: R
authors.initials: R
authors.lastname: Sengers
authors.forename: F
authors.initials: F
authors.lastname: Trijbels
authors.forename: L
authors.initials: L
authors.lastname: van den Heuvel
mesh_terms: D000595:Amino Acid Sequence; D009202:Cardiomyopathies / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D004272:DNA, Mitochondrial; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I