目的:分析1个丙酸血症(propionic acidemia，PA)家系的致病变异。方法:通过多重探针杂交富集患儿n PCCA和n PCCB基因的全部编码外显子及其侧翼区序列进行高通量测序，检测可疑变异，运用Sanger测序在家系中进行变异验证。提取患儿父亲外周血淋巴细胞RNA，应用逆转录-聚合酶链反应联合Sanger测序对新剪切变异进行验证；采用多种在线软件对错义变异进行致病性分析。n 结果:在患儿n PCCB基因第1内含子和第7外显子检出复合杂合变异，分别是c.184-2A>G剪切变异和c.733G>A(p.G245S)错义变异，Sanger测序验证表明二者分别来自父母。mRNA水平验证表明，c.184-2A>G变异可导致n PCCB基因转录产物第2外显子的缺失；多个软件预测c.733G>A错义变异具有致病性，245位置的氨基酸在不同物种均具有高度保守性。n 结论:PCCB基因变异可能是该家系患儿的致病原因，新变异的检出丰富了n PCCB基因的变异谱。n “,”Objective:To detect pathogenic variants in a pedigree affected with propionic acidemia (PA).Methods:The proband was subjected to high-throughput next-generation sequencing. Suspected variants were validated by Sanger sequencing of his family members.mRNA was extracted from peripheral blood lymphocytes from the proband’s father in order to verify the influence of the splicing variant by RT-PCR combined with Sanger sequencing. The pathogenicity of the missense variant was predicted by using PolyPhen-2, MutationTaster, SIFT, COBALT and HOPE software.Results:The proband was found to harbor compound heterozygous variants of the n PCCB gene, namely c. 184-2A>G and c. 733G>A (p.G245S), which were respectively inherited from his father and mother. RT-PCR combined with Sanger sequencing confirmed skipping of exon 2 during transcription. Bioinformatic analysis indicated the c. 733G>A (p.G245S) variant to be damaging.n Conclusion:The two variants of the n PCCB gene probably underlay the disease in this patient. Above findings have enriched the spectrum of n PCCB gene variants.n