摘要目的 研究丙酸血症患儿丙酰辅酶A羧化酶PCCA和PCCB基因突变情况.方法 应用PCR扩增和直接测序对11例丙酸血症患儿PCCA和PCCB基因的各个外显子及其两侧侧翼序列进行突变检测,并对部分患儿父母进行相应突变基因检测.结果 6例为PCCA突变,5例为PCCB突变.共发现13种突变,其中10种突变未见文献报道,突变类型包括错义突变、缺失突变、剪切位点突变和复杂型插入缺失突变,错义突变为最常见类型.167-179dell3insl复杂型插入缺失突变在2例中为纯合突变.结论 在11例内酸血症患儿中检测到13种突变,其中10种为新突变类型,为今后有关丙酸血症的发病机制研究提供理论依据.

abstractsObjective 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 t-PCC and β-PCC subunits.nuclearly encoded by genes PCCA and PCCB,respectively.Mutation in either gene cause propionic acidemia.the PCCA gene is located on chmmosome 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.Methods 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.Results 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 α-PCC subunit while three missense mutations (484G>A,601G>A and 1253C>T)and two short insertion-deletions(167-179dell3insl.560- 561delCCinsT)were found in β-PCC subunit.The 167-179del13insl change was identified in two homozygous PA patients,with allelic frequency of 40%in B-PCC subunit deficiencies.Conclusion Thirteen mutations were found in 11 Chinese PA patients including ten novel mutations.No mutation is predominant in Chinese PCCA and PCCB deficient patients.