糖原累积病Ⅰa型患儿20例基因突变分析与临床研究  

Analysis of gene mutations and clinical manifestations in 20 patients with glycogen storage disease type Ⅰ a

作　　者：梁翠丽[1] 刘丽[1] 盛慧英[1] 江敏妍[1] 尹曦[1] 李秀珍[1] 程静[1] 毛晓健[1] 张文[1] 范莉萍[1] 

机构地区：[1]广州医学院附属广州市妇女儿童医疗中心内分泌代谢科,510623

出　　处：《中华实用儿科临床杂志》2013年第8期581-585,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：“十一五”国家科技支撑计划项目（2006BA105A07）;广州市科技局支撑项目（2010J-E231-1）

摘　　要：目的研究糖原累积病Ⅰa型（GSDIa）患儿葡萄糖-6-磷酸酶催化亚单位基因（G6PC基因）突变情况，探讨基因型与临床表型之间的关系。方法依据临床表现、生化检查及饥饿试验、胰高血糖素刺激试验结果，拟诊出48例肝糖原累积病（LGSD）患儿；应用PCR反应直接测序的方法，对疑似LGSD患儿的G6PC基因外显子及其相邻区域进行突变检测。采用50例无血缘关系的健康儿童作为健康对照，以排除基因多态性；使用DNAMAN软件进行多物种序列同源性比较分析，确定其是否具有保守性。结果48例LGSD患儿中检测到20例患儿存在G6PC基因突变，共检测到8种突变类型，包括1种剪切突变：c．648G〉T，5种错义突变：P．R83H、P．H119L、P．L173P、P．1341N、P．C109Y和2种移码突变：c．262delG、c．260-262delGGinsA。其中c．648G〉T、P．R83H是本组研究最常见的突变，突变频率分别为37．50％、22．50％；P．C109Y、c．260-262delGGinsA为新发突，41．67％（20／48例）拟诊为LGSD的患儿通过G6PC基因分析确诊为GSDⅠa。从临床表现及常规实验室检查分析，20例GSDⅠa患儿均表现为肝大、肝功能异常、高乳酸血症、高三酰甘油血症，88．24％（15／17例）的患儿饥饿试验阳性，82．35％（14／17例）患儿对胰高血糖素刺激试验无反应。结论c．648G〉T、p．R83H为本组GSDIa患儿最常见突变类型，P．C109Y、c．260-262delGGinsA为国内外尚未见报道的新发致病突变。GSDIa基因型不同的患儿均有相似的典型LGSD临床表现。Objective To investigate the glucose-6-phosphatese catalytic （G6PC） unit G6PC gene mutations in patients with liver glycogen storage disease（ LGSD）, and to discuss the relationship of glycogen storage disease type Ⅰ a（ GSD Ⅰ a） genotype and phenotype. Methods According to clinical manifestations,laboratory tests and glucagon test results,48 patients suspected as LGSD were selected in this research. By using PCR combined with direct DNA se- quencing, the entire coding region of the G6PC gene was screened. Fifty healthy children were also investigated as con- trol group. The species homology was analyzed by DNAMAN software to investigate gene conservatism. Results Eight types of G6PC gene mutations were detected in 20 cases of the 48 patients （41.67 %, 20/48 cases）, which were c. 648G 〉 T,p. R83H, p. H119L, p. L173P, p. I341N, c. 260-262delGGinsA, p. C109Y and c. 260-262delGGinsA. Among which, c. 648G 〉 T and p. R83H were the common gene mutations in this study, their mutations frequency were 37.50% and 22.50% ,respectively. p. C109Y and c. 260-262de1GGinsA were novel mutations. All patients with different muta- tions had the same growth retardation, hypoglycemia, hepatomegaly, hyperlipidemia, lactic acidemia. Eighty-eight point twenty-four percent（ 15/17 cases） patients were hypoglycemia when fasted for 6 hours. The low blood sugar in 82.35% （ 14/17 cases） patients was no responsive to glucagon injection. Conclusions In this study,it revealed that c. 648G 〉 T and p. R83H were the most common mutations in our patients. Two new pathogenic mutation types were found, which were p. C109Y and c. 260-262delGGinsA. The patients with different genotypes showed the same typical clinical mani- festations.

关 键 词：糖原累积病 Ⅰa型 葡萄糖-6-磷酸 基因突变 

分 类 号：R72[医药卫生—儿科]