糖原累积病Ⅲa型一家系两例患儿的分子诊断研究

Identification of a novel mutation of AGL gene in two siblings affected with glycogen storage disease typeⅢ a

目的研究糖原累积病IIIa型一家系AGL基因突变特点。方法分析一家系两例疑诊糖原累积病IIIa型患儿的临床资料。分别采集研究对象外周抗凝血标本，提取基因组DNA，然后对AGL基因所有外显子及其侧翼序列进行Sanger测序，以寻找致病突变。然后，通过对75名健康志愿者AGL基因相应外显子的Sanger测序，调查新突变的人群分布频率。结果该家系中姐弟二人均以低血糖及肝脏增大为主要临床特征，伴转氨酶及肌酶明显升高。AGL基因分析显示两患儿均为突变c．1735＋1G〉T和C．9591G〉C的复合杂合子，后一个突变未见文献报道，在正常人群中频率小于1％。结论通过AGL基因分析，结合临床表现，该家系中姐弟二人均确诊为糖原累积病IIIa型患者。新突变c．959—1G〉C的识别扩展了AGL基因突变谱，同时为患儿分子诊断和家系遗传咨询提供了实验依据。

Objective To detect potential mutation of the AGL gene in two siblings affected with glycogen storage disease type []] a. Methods Clinical data of the two siblings was collected and analyzed. Genomic DNA was extracted from peripheral venous blood samples from the patients and their parents. All exons and their flanking sequences of the AGL gene were subjected to PCR amplification and Sanger sequencing. Suspected mutation was verified in 75 healthy controls. Results The main clinical features of the two siblings included hypoglycemia and hepatomegaly, along with markedly elevated liver and myocardial enzymes. Genetic analysis revealed that both siblings harbored compound heterozygous mutations c. 1735- 1G〉T and c. 959-1G〉C of the AGL gene. Among these, the splicing mutation c. 959 1G〉C was a novel one with an allele frequency of 〈1 %. Conclusion Based on their clinical features and genetic analysis, the siblings were diagnosed with glycogen storage disease type Ⅲ a. The c. 959 1G〉C has enriched the spectrum of AGL gene mutations.