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 alpha and beta 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 beta 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 
approximately 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 approximately 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 beta-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.