title: A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome.
abstract: Although deficiency of complex I of the mitochondrial respiratory chain is a frequent cause of encephalopathy in children, only a few mutations have been reported in each of its subunits. In the absence of families large enough for conclusive segregation analysis and of robust functional testing, it is difficult to unequivocally show the causality of the observed mutations and to delineate genotype-phenotype correlations, making additional observations necessary. We observed two consanguineous siblings with an early-onset encephalopathy, medulla, brainstem and mesencephalon lesions on brain magnetic resonance imaging and death before 8 months of age, caused by a complex I deficiency. We used a homozygosity mapping approach and identified a missense mutation in the NDUFV1 gene. The mutation, p.Arg386His, affects a highly conserved residue, contiguous to a cysteine residue known to coordinate an Fe ion. This observation adds to our understanding of complex I deficiency disease. It validates the important role of Arg386 and therefore supports the current molecular model of iron-sulfur clusters in NDUFV1.
authors.affiliation: Department of Medical Genetics, Center of Human Genetics, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Vilain
authors.forename: C
authors.initials: C
authors.lastname: Rens
authors.forename: A
authors.initials: A
authors.lastname: Aeby
authors.forename: D
authors.initials: D
authors.lastname: Balériaux
authors.forename: P
authors.initials: P
authors.lastname: Van Bogaert
authors.forename: G
authors.initials: G
authors.lastname: Remiche
authors.forename: J
authors.initials: J
authors.lastname: Smet
authors.forename: R
authors.initials: R
authors.lastname: Van Coster
authors.forename: M
authors.initials: M
authors.lastname: Abramowicz
authors.forename: I
authors.initials: I
authors.lastname: Pirson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001933:Brain Stem / Q000473:pathology*; D003241:Consanguinity; D042967:Electron Transport Complex I / Q000172:deficiency / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D035781:Siblings
chemical_list: C112232:NDUFV1 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I