DEMONSTRATION OF A NEW PATHOGENIC MUTATION IN HUMAN COMPLEX-I DEFICIENCY - A 5-BP DUPLICATION IN THE NUCLEAR GENE ENCODING THE 18-KD (AQDQ)SUBUNIT

We report the cDNA cloning, chromosomal localization, and a mutation i n the human nuclear gene encoding the 18-kD (AQDQ) subunit of the mito chondrial respiratory chain complex I, The cDNA has an open reading fr ame of 175 amino acids and codes for a protein with a molecular mass o f 23.2 kD. Its gene was mapped to chromosome 5. A homozygous 5-bp dupl ication, destroying a consensus phosphorylation site, in the 18-kD cDN A was found in a complex I-deficient patient. The patient showed norma l muscle morphology and a remarkably nonspecific fatal progressive phe notype without increased lactate concentrations in body fluids, The ch ild's parents were heterozygous for the mutation. In 19 other complex I-deficient patients, no mutations were found in the 18-kD gene.