Mutation analysis of the pyruvate dehydrogenase E1 alpha gene in eight patients with a pyruvate dehydrogenase complex deficiency.

The human pyruvate dehydrogenase complex. Isolation of cDNA clones for the E1 alpha subunit, sequence analysis, and characterization of the mRNA.

cDNA clones corresponding to the entire length of mRNA for the alpha subunit of human pyruvate dehydrogenase (EC 1.2.4.1), the E1 component of the pyruvate dehydrogenase complex, have been isolated from liver cDNA libraries. Two classes of cDNA clones were obtained and these correspond to two forms of pyruvate dehydrogenase E1 alpha mRNA. Both mRNA species have been demonstrated in a variety of...

Defects in the E2 lipoyl transacetylase and the X-lipoyl containing component of the pyruvate dehydrogenase complex in patients with lactic acidemia.

Three patients with chronic lacticacidemia and deficiency of the pyruvate dehydrogenase complex demonstrated in cultured skin fibroblasts showed abnormalities on Western blotting with anti-pyruvate dehydrogenase complex antiserum which were not located in the E1 (alpha and beta) component of the complex. One of these patients had an enzymatically demonstrable deficiency in the E2 dihydrolipoyl ...

Heterogeneous expression of protein and mRNA in pyruvate dehydrogenase deficiency.

Deficiency of pyruvate dehydrogenase [pyruvate:lipoamide 2-oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1], the first component of the pyruvate dehydrogenase complex, is associated with lactic acidosis and central nervous system dysfunction. Using both specific antibodies to pyruvate dehydrogenase and cDNAs coding for its two alpha and beta subunits, we characterized pyru...

Mutation Analysis of the Pyruvate Dehydrogenase Exa Gene in Eight Patients With a Pyruvate Dehydrogenase Complex Deficiency

X chromosome inactivation and the diagnosis of X linked disease in females.

In studies of female patients with suspected deficiency of the E1 alpha subunit of the pyruvate dehydrogenase complex, we have found that X inactivation ratios of 80:20 or greater occur at sufficient frequency in cultured fibroblasts to make exclusion of the diagnosis impossible in about 25% of cases. Pyruvate dehydrogenase E1 alpha subunit deficiency is an X linked inborn error of metabolism w...