Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia

Abstract Propionic acidemia (PA) is an inborn error of organic acid metabolism caused by a deficiency of propionyl-CoA carboxylase. This enzyme is composed of two non-identical subunits, α and β, which are encoded by the PCCA and PCCB genes, respectively. An enzyme deficiency can result from mutations in either PCCA or PCCB . To elucidate the mutation spectrum in Japanese patients, we have performed a mutation analysis of 30 patients with PA, which included nine previously reported patients. The study revealed that 15 patients were α-subunit deficient and 15 patients were β-subunit deficient. Seven novel mutations were found (IVS18 − 6C > G, 1746G > A, C398R, G197E and IVS18 + 1G > A in the PCCA ; A153P and IVS9 + 1G > T in the PCCB ). Among these Japanese patients with α-subunit deficiencies, 923–924insT, IVS18 − 6C > G, and R399Q mutations were frequent and the total allelic frequency of these three mutations combined was 56% (17/30). This is in sharp contrast to the mutation spectrum found in Caucasian patients, where no prevalent mutations have been identified. Among the β-subunit deficiencies, there were three frequent mutations; R410W, T428I, and A153P, whose allelic frequencies were 30, 26.7, and 13.3%, respectively. In conclusion, a limited number of mutations are predominant in both PCCA and PCCB genes among Japanese patients with propionic acidemia.