论文部分内容阅读
目的探讨1例临床疑似糖原累积病Ⅱ型患儿的临床特点和酸性-α-葡萄糖苷酶(GAA)基因突变情况。方法分析患儿病史,并检测患儿及其父母外周血白细胞酸性-α-葡萄糖苷酶活性,聚合酶链反应(polymerase chain reaction,PCR)扩增GAA编码区,直接测序分析GAA基因突变情况。结果该患儿生后2个月即出现喂养困难和全身肌无力,4个月发现心脏增大,6个月时死于心肺功能衰竭。患儿白细胞酸性-α-葡萄糖苷酶活性明显降低,仅为正常对照中位数的17.3%。DNA测序分析显示患儿携带一个新无义突变p.W738X和一个已报道的p.E888X突变。患儿及其母亲均携带假性缺陷等位基因c.[1726G>A;2065G>A]。结论 GAA酶活性测定结合基因诊断明确诊断1例临床疑似糖原累积病(GSD)Ⅱ型,发现1个GAA基因新无义突变p.W738X。根据患儿临床表现可诊断为婴儿型GSDⅡ,推测p.W738X突变对GAA酶活性影响严重。由于假性缺陷等位基因c.[1726G>A;2065G>A]可引起正常人GAA酶活性降低,故GAA基因突变分析对明确GSDⅡ型患者的诊断及其家系的产前诊断有重要意义。
Objective To investigate the clinical features and the mutation of acid-α-glucosidase (GAA) gene in 1 case of clinical suspected glycogen storage disease type Ⅱ. Methods The history of children was analyzed. The activity of acid-α-glucosidase in peripheral blood leukocytes of children and their parents was detected. The GAA coding region was amplified by polymerase chain reaction (PCR) and the GAA gene mutation was analyzed by direct sequencing. Results The patient developed difficulty in feeding and generalized muscular weakness 2 months after birth. The heart was found to be enlarged at 4 months and died of cardiorespiratory failure at 6 months. Children with leukocyte acid-α-glucosidase activity was significantly lower, only the normal control median of 17.3%. DNA sequencing analysis showed that children had a new nonsense mutation p.W738X and a reported p.E888X mutation. Both children and their mothers carry the pseudo-defective allele c. [1726G> A; 2065G> A]. Conclusions The GAA enzyme activity assay combined with gene diagnosis clearly diagnosed one case of clinically suspected glycogen storage disease (GSD) type Ⅱ, and a new nonsense mutation of GAA gene was found in p.W738X. According to the clinical manifestations of children can be diagnosed as infant GSD Ⅱ, presumably p.W738X mutation on the GAA enzyme activity. GAA gene mutation analysis plays an important role in determining the diagnosis of GSDⅡpatients and prenatal diagnosis of their pedigrees, because the false negative allele c. [1726G> A; 2065G> A] can cause the decrease of GAA activity in normal subjects.