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An Unusual Insertion/Deletion in the Gene Encoding the β-Subunit of Propionyl-CoA Carboxylase is a Frequent Mutation in Caucasian Propionic Acidemia

Takahiro Tahara, Jan P. Kraus and Leon E. Rosenberg
Proceedings of the National Academy of Sciences of the United States of America
Vol. 87, No. 4 (Feb., 1990), pp. 1372-1376
Stable URL: http://www.jstor.org/stable/2353837
Page Count: 5
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
An Unusual Insertion/Deletion in the Gene Encoding the β-Subunit of Propionyl-CoA Carboxylase is a Frequent Mutation in Caucasian Propionic Acidemia
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Abstract

Propionic acidemia is an inherited disorder of organic acid metabolism that is caused by deficiency of propionyl-CoA carboxylase (PCC;EC 6.4.1.3). Affected patients fall into two complementation groups, pccA and pccBC (subgroups B, C, and BC), resulting from deficiency of the nonidentical α and β subunits of PCC, respectively. We have detected an unusual insertion/deletion in the DNA of patients from the pccBC and pccC subgroups that replaces 14 nucleotides in the coding sequence of the β subunit with 12 nucleotides unrelated to this region of the gene. This results in elimination of an Msp I restriction site, a 2-base-pair (bp) deletion, a frameshift, and a stop codon in the new frame ≈ 100 amino acid residues proximal to the normal carboxyl terminus. Among 14 unrelated Caucasian patients in the pccBC complementation group, this unique mutation was found in 8 of 28 mutant alleles examined. Mutant allele-specific oligonucleotide hybridization to amplified genomic DNAs revealed that the inserted 12 nucleotides do not originate in an ≈ 1000-bp region around the mutation. In the course of our investigation, we identified another mutation in the same exon: a 3-bp in-frame deletion that eliminates one of two isoleucine codons immediately preceding the Msp I site. Two unrelated patients were compound heterozygotes for this single-codon deletion and for the insertion/deletion described above. We conclude that either there is a propensity for the PCC β-subunit gene to undergo mutations of this sort at this position or, more likely, the mutations in all of the involved Caucasian patients have a common origin in preceding generations.

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