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
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
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.