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目的对中国大陆地区幼年起病的晚发型糖原贮积症Ⅱ型(GSDⅡ,Pompe 病)患者进行临床和基因突变分析。方法对2例幼年起病的 Pompe 病患儿进行临床分析,提取患儿皮肤成纤维细胞及其父母的外周血 DNA,应用聚合酶链反应(PCR)扩增α-1,4-葡萄糖苷酶的19个外显子,测序,进行突变检测。同时对50例健康对照100个等位基因进行15号外显子的 PCR 扩增,测序,确定突变特征。结果 1例临床表现为进行性近端肌肉无力,肌张力低下;1例表现为肌容积减少,呼吸肌受累;2例均有肌酸磷酸肌酶升高,肌电图提示肌源性损害,肌活检呈空泡性改变,皮肤成纤维细胞α-1,4-葡萄糖苷酶活性测定明显低下。突变检测:测序发现4个杂合错义突变,例1为 c796 C>T,p.266Pro>Ser;c2105 G>A,p.702Arg>His;例2为 c2132 C>G,p.711Thr>Arg;c2167 G>A,p.723Val>Met。其中后3个为新突变,50例健康对照100个等位基因测序未发现同样突变。结论幼年起病的 Pompe 病患儿临床表现存在差异,呼吸肌受累情况影响其预后;检测到3个错义新突变,可能为致病突变。
Objective To analyze the clinical and gene mutation of late onset glycogen storage disease type Ⅱ (Pompe disease) in juvenile Chinese mainland. Methods The clinical data of 2 children with Pompe disease were collected. The peripheral blood DNA of children’s skin fibroblasts and their parents were extracted. Polymerase chain reaction (PCR) was used to amplify α-1,4-glucosidase Nineteen exons were sequenced and subjected to mutation detection. At the same time, 50 healthy controls 100 alleles were exon 15 PCR amplification, sequencing, to determine the mutation characteristics. Results One patient had progressive proximal muscular weakness and low muscle tension. One patient showed decreased muscle volume and respiratory muscle involvement. Both patients had elevated creatine phosphokinase and electromyogram showed myogenic damage. Biopsy showed vacuolar changes in skin fibroblasts α-1,4-glucosidase activity was significantly lower. Mutation detection: 4 heterozygous missense mutations were found by sequencing. Example 1 was c796 C> T, p.266Pro> Ser; c2105 G> A, p.702 Arg> His; Example 2 was c2132 C> Arg; c2167 G> A, p.723 Val> Met. The latter three were new mutations and the same mutation was not found in 100 alleles of 50 healthy controls. Conclusion The clinical manifestations of children with Pompe disease are different in infancy. The involvement of respiratory muscles affects their prognosis. Three new missense mutations were detected, which may be pathogenic mutations.