以肝肿大为主要表现的Ⅰa型糖原累积病家系研究分析

Glycogen storage disease typeⅠa:a pedigree study

目的对一个以肝肿大为主要表现的Ⅰa型糖原累积病(GSDⅠa)家系进行基因突变研究和分析。方法收集GSDⅠa患者家系资料和亲属外周血标本,PCR法扩增葡萄糖-6-磷酸酶(G-6- Pase)基因的5个外显子,并测序比对基因序列的变化。结果结合临床表现、肝组织学检查及家系分析,患者诊断明确。基因结构分析显示,患者G-6-Pase基因5号外显子密码727G→T/1071G→A(A331E)复合突变。在其父辈家系中存在5号外显子727G→T杂合子突变.导致剪切点突变;其母辈家系中存在5号外显子1071G→A杂合子突变,导致第331位密码子编码的A转变为E。结论患者的祖父及外祖母为首发突变者。727G-T/1071G→A(A331E)复合突变是该家系发病的分子生物学其础。

Objective To analyze the symptoms of glycogen storage disease type Ⅰa（GSD Ⅰ a） and the background of those associated genes. Methods The clinical data and blood samples from a GSD Ⅰ a pedigree were collected and the change of G-6-Pase gene were analized by polymerase chain reaction（PCR）. Results Diagnosis of the GSD Ⅰ a patient was made by the clinical manifestation and the liver biopsy. The complex mutation 727G→T/1071C→A（A331E） in exon 5 was found in the GSD I a patient. The heterozygote mutation of 727G→T was found in agnate pedigree and the 1071C→A（A331E） heterozygote mutation was found in the maternal pedigree. Conclusions The GSD Ⅰ a patient＇s agnate grandfather and maternal grandmother are the first two persons with the point mutations and the complex mutation caused a series of consequence. The gene study could be regarded as the molecular base of the antenatal diagnosis.