两例AGL基因复合杂合变异导致糖原累积症Ⅲ型患儿的遗传学分析  

Analysis of two cases of glycogen storage disease typeⅢdue to compound heterozygous variants of AGL gene

作　　者：张猛 王昶 谢桢 吴成 龙云 Zhang Meng;Wang Chang;Xie Zhen;Wu Cheng;Long Yun(Department of Gastroenterology,Anhui Provincial Children’s Hospital,Hefei,Anhui 230051,China;Department of Radiology,Anhui Provincial Children’s Hospital,Hefei,Anhui 230051,China;Ultrasonography Unit,Anhui Provincial Children’s Hospital,Hefei,Anhui 230051,China)

机构地区：[1]安徽省儿童医院消化内科,合肥230051 [2]安徽省儿童医院医学影像中心,合肥230051 [3]安徽省儿童医院B超室,合肥230051

出　　处：《中华医学遗传学杂志》2021年第11期1073-1076,共4页Chinese Journal of Medical Genetics

摘　　要：目的对2例AGL基因变异导致糖原累积症Ⅲ型(glycogen storage disease typeⅢ,GSDⅢ)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。Objective To explore the clinical features and genetic basis of two children with glycogen storage disease typeⅢ(GSDⅢ).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 GSDⅢ.Literature review suggested that the main type variant among Chinese patients with GSDⅢinvolve 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 GSDⅢin both children.Above findings have enriched the spectrum of genetic variants underlying this disease.

关 键 词：糖原累积症Ⅲ型 AGL基因 剪接位点变异 

分 类 号：R725[医药卫生—儿科]