[Gene mutation analysis in patients with propionic acidemia].

Propionic acidemia is a common organic acidemia, caused by deficiency of propionyl-CoA carboxylase (PCC), which catalyzes the carboxylation of propionyl-CoA to D-methylmalonyl-CoA. PCC is a dodecameric enzyme of alpha-PCC and beta-PCC subunits, nuclearly encoded by genes PCCA and PCCB, respectively. Mutation in either gene cause propionic acidemia, the PCCA gene is located on chromosome 13q32 with 24 exons and the PCCB gene is located on chromosome 3q13.2-q22 with 15 exons. In this study, we analyzed gene mutations of 11 PCCA and PCCB deficient patients from China and to explore the possible mutation spectrum.All 39 exons of PCCA and PCCB genes in 11 unrelated Chinese PA patients were analyzed by polymerase chain reaction (PCR) and direct sequencing. Genomic DNA was extracted using phenol-chloroform method from the peripheral blood leukocytes of each patient. PCR amplification products were checked by 1.8% agarose gel electrophoresis and were subsequently sequenced with ABI 3700 Automated DNA Sequencer.The authors identified 13 PA mutations, 8 affecting the PCCA gene, 5 affecting the PCCB gene, including 10 novel mutations and 3 previously reported mutations. Three missense mutations (1079T > G, 1102G > C and 1850T > C), one splicing mutation (716-2A > G) and one short deletion (1863delA) were found in alpha-PCC subunit while three missense mutations (484G > A, 601G > A and 1253C > T) and two short insertion-deletions (167-179del13ins1, 560-561delCCinsT) were found in beta-PCC subunit. The 167-179del13ins1 change was identified in two homozygous PA patients, with allelic frequency of 40% in beta-PCC subunit deficiencies.Thirteen mutations were found in 11 Chinese PA patients including ten novel mutations. No mutation is predominant in Chinese PCCA and PCCB deficient patients.