title: Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency.
abstract: The human pyruvate dehydrogenase complex catalyses the oxidative decarboxylation of pyruvate to acetyl-CoA. Defects in several of the seven subunits have been reported, but the majority of mutations affect the E1 component and especially the E1 alpha subunit. However, the clinical presentation of patients with pyruvate dehydrogenase E1 alpha deficiency is extremely variable. Dependency of the brain on pyruvate dehydrogenase activity and localization of the gene for the somatic form of the pyruvate dehydrogenase E1 alpha subunit to the X chromosome provide the basis for a better understanding of the variation in the clinical manifestations. Further understanding of the function and interaction of subunits and the pathophysiology of pyruvate dehydrogenase deficiency necessitates the characterization of mutations in the pyruvate dehydrogenase complex. We report the analysis of three patients with pyruvate dehydrogenase E1 alpha deficiency. One female has a three base pair deletion which affects dephosphorylation of the subunit. Of two males analysed, one has a two base pair deletion causing a shift in the reading frame. The other has a base change, resulting in an Arg to His substitution. All three mutations are located near the carboxyl terminus of the subunit.
authors.affiliation: Murdoch Institute for Research into Birth Defects, Royal Children's Hospital, Melbourne, Victoria, Australia.
authors.forename: L L
authors.initials: LL
authors.lastname: Hansen
authors.forename: G K
authors.initials: GK
authors.lastname: Brown
authors.forename: D M
authors.initials: DM
authors.lastname: Kirby
authors.forename: H H
authors.initials: HH
authors.lastname: Dahl
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease; D014960:X Chromosome
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D004247:DNA