The molecular defect in propionic acidemia: exon skipping caused by an 8-bp deletion from an intron in the PCCB allele.

Abstract

Propionic acidemia is an autosomal recessive metabolic disease resulting from a deficiency of propionyl CoA carboxylase (PCC) activity. To investigate the genetic basis of propionic acidemia, we isolated a cDNA encoding the precursor of the beta subunit of human PCC (beta PCC). The cloned cDNA sequence was 1,832 bp long and the open reading frame of 1,617 nucleotides encoded a polypeptide of 539 amino acids with a molecular mass of 58,202 Da. The human beta PCC sequence shared a high degree of homology (91%) with the full-length cDNA of rat beta PCC at the amino acid level; there were only 47 differences among 539 amino acid residues compared. Polymerase chain reaction amplification and sequencing of cDNA from a beta subunit-deficient Japanese patient revealed a deletion of 101 nucleotides consisting of one exon from mature mRNA. This deletion resulted in a frameshift and a stop codon in the new frame. Analysis of the genomic DNA revealed a homozygous 8-bp deletion from bp3 to bp10 of the intron just downstream of the deleted exon. This deletion disrupted the consensus 5' splice signal and led to exon skipping.

• Authors: T Ohura, M Ogasawara, H Ikeda, K Narisawa, K Tada
• Journal: Human genetics (Hum Genet) Vol. 92 Issue 4 Pg. 397-402 (Oct 1993) ISSN: 0340-6717 [Print] Germany
• PMID: 8225321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Propionates
• RNA, Messenger
• DNA
• Ligases
• Carbon-Carbon Ligases
• propionyl CoA carboxylase (ATP-hydrolyzing)

Topics

• Alleles
• Amino Acid Metabolism, Inborn Errors (enzymology, genetics)
• Amino Acid Sequence
• Base Sequence
• Carbon-Carbon Ligases
• Cell Line
• Cells, Cultured
• Chromosome Deletion
• DNA (analysis)
• Exons (genetics)
• Female
• Fibroblasts (cytology)
• Frameshift Mutation
• Humans
• Introns (genetics)
• Ligases (deficiency, genetics)
• Molecular Sequence Data
• Polymerase Chain Reaction
• Propionates (blood)
• RNA, Messenger (analysis)
• Skin (cytology)