Propionyl CoA carboxylase (PCC) is a mitochondrial, biotin-dependent enzyme 
involved in the catabolism of amino acids, odd-chain fatty acids, and other 
metabolites. PCC consists of two subunits, alpha and beta, encoded by the PCCA 
and PCCB genes, respectively. Inherited PCC deficiency due to mutations in 
either gene results in propionic acidemia (PA), an autosomal recessive disease. 
Surprisingly, PA is highly prevalent among Inuits in Greenland. We have analyzed 
reverse transcriptase-PCR products of the beta-subunit mRNA, to characterize the 
responsible mutation(s). A 3-bp insertion, 1540insCCC, was found in homozygous 
form in three patients and in compound heterozygous form in one patient. The 
resulting PCC has no measurable activity, and the mutant beta-subunit appears to 
be very unstable. To test the hypothesis that a common mutation is responsible 
for PA in the Greenlandic Inuit population, 310 anonymous DNA samples of Inuit 
origin were screened for 1540insCCC. We found a carrier frequency of 5%, which 
is very high compared with those of most other autosomal recessive diseases. 
Analysis of alleles of a very closely linked marker, D3S2453, revealed a high 
degree of linkage disequilibrium between one specific allele and 1540insCCC, 
suggesting that this mutation may be a founder mutation.