Characterization of the human complex INDUFB7 and 17.2-kDa cDNAs and mutational analysis of 19 genes of the HP fraction in complex I-deficient-patients

Citation
R. Triepels et al., Characterization of the human complex INDUFB7 and 17.2-kDa cDNAs and mutational analysis of 19 genes of the HP fraction in complex I-deficient-patients, HUM GENET, 106(4), 2000, pp. 385-391
Citations number
40
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN GENETICS
ISSN journal
03406717 → ACNP
Volume
106
Issue
4
Year of publication
2000
Pages
385 - 391
Database
ISI
SICI code
0340-6717(200004)106:4<385:COTHCI>2.0.ZU;2-G
Abstract
Deficiency of NADH:ubiquinone oxidoreductase, the first enzyme complex of t he mitochondrial respiratory chain, is one of the most frequent causes of h uman mitochondrial encephalomyopathies. A relatively small percentage of hu man complex I deficiency is associated with mitochondrial DNA mutations. cD NA characterization and mutational analysis of the structural complex I gen es in 19 complex I-deficient patients, in whom common mtDNA mutations have been excluded, has so far revealed five patients with alterations in evolut ionary conserved nuclear-encoded proteins. In order to complete our knowled ge about the expected 36 structural nuclear complex I genes, we characteriz ed the NDUFB7 and the 17.2-kDa cDNA sequences of the hydrophobic (HP) fract ion of the complex. Subsequently, we screened all subunits of this fraction for the presence of mutations in those 14 patients of our initial patient cohort in whom the underlying genetic cause had not been elucidated. Striki ngly, no pathogenic mutations were found in the HP subunits that would expl ain the complex I deficiency in our patients. Other strategies are needed t o unravel proteins involved in the pathogenesis of the complicated cellular network of transcription until correct assemblage of complex I.