The molecular defect in propionic acidemia: exon skipping caused by an 8-bp deletion from an intron in the PCCB allele.
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Ohura T, Ogasawara M, Ikeda H, Narisawa K, Tada K
The molecular defect in propionic acidemia: exon skipping caused by an 8-bp deletion from an intron in the PCCB allele.
Hum Genet. 1993 Oct;92(4):397-402.
- PubMed ID
- 8225321 [ View in PubMed]
- 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.