title: Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift.
abstract: A patient with lactic acidosis showed a lowered pyruvate dehydrogenase E1 activity and fatigued on slight exercise. The cDNA encoding the pyruvate dehydrogenase E1 alpha-subunit from his lymphocytes, transformed by infection of Epstein-Barr virus, was cloned and sequenced. The nucleotide sequence determination revealed that the gene had a deletion of four nucleotides at the second codon upstream from the termination codon. This deletion would lead to a reading-frame shift and make a new termination codon at the 33d codon downstream from the "normal" termination codon. An S1 nuclease-protection experiment confirmed the presence of mRNA with its deletion in the patient. Amplification, by the polymerase chain reaction method, of the genomic-DNA region from his peripheral blood cells showed that the deletion was localized in an exon and that it was not caused by an abnormal splicing at the intron/exon junction. This is the first report on cloning a defective gene of the pyruvate dehydrogenase complex.
authors.affiliation: Department of Biochemistry, Jichi Medical School, Tochigi-ken, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Endo
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Narisawa
authors.forename: K
authors.initials: K
authors.lastname: Tada
authors.forename: Y
authors.initials: Y
authors.lastname: Kagawa
authors.forename: S
authors.initials: S
authors.lastname: Ohta
mesh_terms: D000140:Acidosis, Lactic / Q000201:enzymology / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000235:genetics; D004720:Endonucleases; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease; D012333:RNA, Messenger / Q000235:genetics; D015719:Single-Strand Specific DNA and RNA Endonucleases
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D012333:RNA, Messenger; D004247:DNA; D004720:Endonucleases; D015719:Single-Strand Specific DNA and RNA Endonucleases