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: H Endo, K Hasegawa, K Narisawa, K Tada, Y Kagawa, S Ohta
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 44 Issue 3 Pg. 358-64 (Mar 1989) ISSN: 0002-9297 [Print] United States
• PMID: 2537010 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pyruvate Dehydrogenase Complex
• RNA, Messenger
• DNA
• Endonucleases
• Single-Strand Specific DNA and RNA Endonucleases

Topics

• Acidosis, Lactic (enzymology, genetics)
• Amino Acid Sequence
• Base Sequence
• Child
• DNA (genetics)
• Endonucleases
• Humans
• Male
• Molecular Sequence Data
• Mutation
• Pyruvate Dehydrogenase Complex (genetics)
• Pyruvate Dehydrogenase Complex Deficiency Disease
• RNA, Messenger (genetics)
• Single-Strand Specific DNA and RNA Endonucleases