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目的:对1例临床疑诊3-甲基巴豆酰辅酶A羧化酶缺乏症(3-methylcrotonyl-coenzyme A carboxylase deficiency，MCCD )患儿及其父母进行基因变异分析，寻找该家系的致病变异，为临床诊断提供分子遗传学依据。方法:抽提先证者及其父母的外周血基因组DNA，应用全外显子组基因测序技术对疑似为MCCD疾病的先证者进行致病基因筛查。根据高通量测序结果，对先证者及其父母进行变异位点的Sanger测序验证分析。应用计算机软件预测变异位点氨基酸进化保守性和变异可能导致的蛋白质结构和功能变化，分析变异位点的性质。结果:Sanger测序结果显示先证者为n MCCC2基因c.1342G>A(p.Gly448Ala)纯合错义变异，为未报道过的新变异。先证者母亲为c.1342G>A(p.Gly448Ala)杂合变异携带者，父亲未检测到该变异。用PolyPhen-2和Mutation Taster软件预测该变异为致病性，变异区域序列在不同物种间高度保守。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南，MCCC2基因c.1342G>A(p.Gly448Ala)变异判定为可能致病性变异(PM2＋PP2～PP5)。n 结论:先证者n MCCC2基因c.1342G>A(p.Gly448Ala)纯合错义变异是其分子发病机制，基因变异分析有助于明确临床诊断。n “,”Objective:To explore the genetic basis for a child with clinically suspected 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD).Methods:Genomic DNA was extracted from peripheral blood samples of the proband and her parents. Whole exome sequencing was used to screen pathogenic variant in the proband. Suspected variant was verified by Sanger sequencing. Impact of the variant on the structure and function of protein product was analyzed by using bioinformatic software.Results:Sanger sequencing showed that the proband has carried homozygous missense c. 1342G>A (p.Gly448Ala) variant of then MCCC2 gene, for which her mother was a heterozygous carrier. The same variant was not detected in her father. The variant was predicted to be pathogenic by PolyPhen-2 and Mutation Taster software, and the site was highly conserved among various species. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c. 1342G>A(p.Gly448Ala) variant ofn MCCC2 gene was predicted to be likely pathogenic(PM2+ PP2-PP5).n Conclusion:The homozygous missense variant of the n MCCC2 gene c. 1342G>A (p.Gly448Ala) probably underlay the molecular pathogenesis of the proband. Genetic testing has confirmed the clinical diagnosis.n