摘要目的:对2例 AGL基因变异导致糖原累积症Ⅲ型(glycogen storage disease type Ⅲ，GSD Ⅲ)患儿的临床特征与遗传学进行分析，明确其可能的致病原因。 方法:应用医学外显子组家系检测对患儿及双亲进行基因检测，并通过相关生物信息学预测分析变异的生物学危害性。结果:基因检测结果显示两例患儿 AGL基因均发生了复合杂合变异，患儿1的 AGL基因存在c.1423+1G>A和c.3701-2A>G复合杂合变异，患儿2的 AGL基因存在c.4213_4214insA(p.Glu1405Glufs*17)和c.3589-3C>G复合杂合变异，结合生物信息学预测分析3个剪接位点变异均影响正常的剪接。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， AGL基因c.1423+1G>A、c.3701-2A>G和c.4213_c.4214insA变异均评定为致病(PVS1+PM2+PM3，PVS1+PM2+PM3，PVS1+PM2+PP5)，c.3589-3C>G变异评级为意义不明(PM2+PM3+PP3)。 结论:AGL基因复合杂合变异可能是导致两例患儿发病的原因，新变异的检出拓展了 AGL基因的变异谱。

abstractsObjective:To explore the clinical features and genetic basis of two children with glycogen storage disease type Ⅲ (GSD Ⅲ).Methods:The probands and their parents were subjected to genetic testing, and the pathogenity of candidate variants was analyzed by using bioinformatic tools.Results:Sequencing has identified compound heterozygous variants of the AGL gene in both children, namely c. 1423+ 1G>A and c. 3701-2A>G in case 1, and c. 4213_c.4214insA (p.Glu1405Glufs*17) and c. 3589-3C>G in case 2. Both children were diagnosed with GSD Ⅲ. Literature review suggested that the main type variant among Chinese patients with GSD Ⅲ involve splice sites of the AGL gene, with c. 1735+ 1G>T being the most common. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.1423+ 1G>A, c. 3701-2A>G and c. 4213_c.4214insA variants of AGL gene were predicted to be of pathogenic(PVS1+ PM2+ PM3, PVS1+ PM2+ PM3, PVS1+ PM2+ PP5), and c. 3589-3C>G variant was predicted to be of uncertain significance(PM2+ PM3+ PP3). Conclusion:The compound heterozygous variants of the AGL gene probably underlay the GSD Ⅲ in both children. Above findings have enriched the spectrum of genetic variants underlying this disease.