title: Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the E1 alpha subunit.
abstract: We report the molecular characterization of a case of a functional PDH-E1 (E1 subunit of pyruvate dehydrogenase) deficiency, a cause of severe congenital lactic acidosis. Residual PDH-E1 activity was reduced to 10% of normal values, although the subunit appeared to be quantitatively and qualitatively normal at the protein level as determined by Western blotting. The sequence of PDH-E1 alpha mRNA and the corresponding genomic DNA revealed an in-frame 21-bp insertion between codons 305 and 306 of the normal E1 alpha cDNA. The mutational insert commences with a novel GAT codon and is a nearly perfect tandem duplication of the wild type DNA sequence. A serine phosphorylation site regulating the activity of the PDH complex is altered by this insertion, which in all likelihood is responsible for the functional enzymatic deficiency leading to lactic acidosis.
authors.affiliation: Laboratory of Medical Genetics, Vrije Universiteit Brussel (VUB), Belgium.
authors.forename: L
authors.initials: L
authors.lastname: De Meirleir
authors.forename: W
authors.initials: W
authors.lastname: Lissens
authors.forename: E
authors.initials: E
authors.lastname: Vamos
authors.forename: I
authors.initials: I
authors.lastname: Liebaers
mesh_terms: D000140:Acidosis, Lactic / Q000151:congenital / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D030481:Pyruvate Dehydrogenase (Lipoamide); D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D012333:RNA, Messenger; D004247:DNA; D030481:Pyruvate Dehydrogenase (Lipoamide)