Propionyl-CoA carboxylase (PCC) is a mitochondrial, biotin-dependent enzyme 
involved in the catabolism of branched chain amino acids, odd chain fatty acids, 
and other metabolites. PCC consists of non-identical subunits, alpha and beta, 
encoded by the PCCA and PCCB genes, respectively. Inherited deficiency of PCC 
due to mutations in either the PCCA or the PCCB gene results in propionic 
acidemia (PA), a clinically heterogeneous disorder with a severe, often lethal, 
neonatal form, and a mild, later onset form. To characterize PCCA gene mutations 
responsible for PCC deficiency, we analyzed RT-PCR products obtained from 
cultured fibroblasts from Spanish PCC-alpha deficient patients. In three 
patients, smaller than normal PCR products were observed, and sequence analysis 
revealed the deletion of a 54-bp exon in the cDNA. Sequencing of genomic DNA 
from these three patients led to the identification of three novel mutations in 
the PCCA gene, two short deletions and one small insertion, adjacent to short 
direct repeats, and all of them affecting the consensus splice sites of the 
skipped exon. These mutations, 1771IVS-2del9, 1824IVS+3del4, and 1824IVS+3insCT, 
are the cause of the aberrant splicing of the PCCA pre-mRNA and result in an 
in-frame deletion of 54 nucleotides in the cDNA, probably leading to an unstable 
protein structure which is responsible for the lack of activity leading to PCC 
deficiency in these patients.