Propionic acidemia is an inborn error of metabolism resulting from a deficiency 
of propionyl-CoA carboxylase activity. The alpha- and beta-subunits of the 
enzyme are encoded by the PCCA and PCCB genes, respectively. Using direct 
sequencing and restriction digests of amplified reverse transcripts and genomic 
DNA, we have identified two mutations of the PCCB gene in a propionic acidemia 
patient from the pccC complementation subgroup (the PCCB gene contains the major 
complementation group pccBC and subgroups pccB and pccC). One of the proband 
alleles contains an inframe 3-bp deletion inherited from the father which 
results in the deletion of an isoleucine residue in the beta-subunit of the 
enzyme. The other mutant allele, inherited from the mother, has a 14-bp deletion 
and an addition of 12 bp of new sequence at the same site as the father's 
allele. The inserted sequence is a partial duplication of a sequence just 
upstream of the mutation site. The net result of this mutation generates a 
frameshift and a downstream stop codon. Examination of fibroblast mRNA from the 
patient showed that it consists essentially of the father's sequence, making it 
effectively the only expressed allele for the beta-protein. A survey of 
additional patient cell lines revealed the insertion/deletion rearrangement in 
three additional patients, two from the pccBC group and one unclassified. The 
3-bp deletion allele was unique to the proband. The identification of two 
distinct alleles occurring at the same site in the PCCB gene underscores the 
importance of this site in enzyme function or integrity.