糖原贮积症Ⅲ型基因突变的初步研究  

Mutation analysis of glycogen debrancher enzyme gene in five Chinese patients with glycogen storage disease type Ⅲ

作　　者：庄太凤[1] 邱正庆[1] 魏珉[1] 黄尚志[2] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院儿科,100730 [2]中国医学科学院基础医学研究所医学遗传学系,100730

出　　处：《中华儿科杂志》2005年第2期85-88,共4页Chinese Journal of Pediatrics

摘　　要：　目的　对糖原贮积症Ⅲ型(GSDⅢ)及其缺陷酶 (糖原脱支酶 )进行临床和基因突变分析。方法　对 6例临床疑诊为GSDⅢ患儿进行临床分析,并对患儿及其父母的外周血DNA,应用PCR扩增糖原脱支酶的 33个外显子,测序。结果　GSDⅢ的临床表现为肝脾肿大、低血糖、高血脂、生长迟缓、肝转氨酶升高和酸中毒,肾上腺素刺激试验符合GSDⅢ,生玉米淀粉治疗可以改善病情。对糖原脱支酶基因的外显子PCR产物直接测序:患儿 1未发现突变;患儿 2为外显子 8 (父源 1294C>T,L298L)和外显子 34(母源 4747G>T,E1450X)复合杂合突变;患儿 3为外显子 8(父源 1294C>T,L298L)和外显子 3(母源 10G>A)复合杂合突变;患儿 4为外显子 35纯合突变 (4664insCT);患儿 5为外显子 16(父源 2341delGCCATAGA,移码突变)和外显子 10(母源 1559G>A,R387Q)复合杂合突变;患儿 6为外显子 26(父源 3742G>A,G1115R)和外显子 12(母源 1686T>G,Y429X)复合杂合突变。结论　GSDⅢ临床表现多样,基因分析发现新的糖原脱支酶基因突变类型。Objective Type Ⅲ glycogen storage disease (GSD-Ⅲ, McKusick 232400), is a rare autosomal recessive disorder, also known as Cori′s or Forbe′s disease.The affected enzy me is amylo-1,6-glucosidase, 4-alpha-glucanotransferase (glycogen debrancher enzyme, GDE or amylogluco- sidase,AGL), which is responsible for the debranchi ng of the glycogen molecule during catabolism. The AGL gene is located on chromo some 1p21 and contains 35 exons translated in a monomeric protein product. The c linical manifestations of GSD-Ⅲ are represented by hepatomegaly, recurrent hyp oglycemia, seizures, growth failure, dysmorphism, hyperlipidemia, raised transam inases and creatine kinase concentrations and, in a number of subjects, myopathy and cardiomyopathy. The hepatocellular adenoma, hepatocellular carcinoma, diabe tes mellitus and liver fibrosis remain rare events. The diagnosis of debrancher deficiency was established by laboratory tests, electromyography (EMG), and muscle and liver biopsy. Methods We studied six GSD-Ⅲ families after patients or parental consent an d the clinical characteristics were documented. Analysis of 33 exons and part ex on-intron boundaries of the AGL gene in patients and their parents were carried out by PCR and direct DNA sequencing. Results The clinical features included hepatomegaly, splenomegaly, recurrent hypoglycemia, hyperlipidemia, growth failure, raised transaminases and acidosis . Administration of epinephrine 2 hours after a carbohydrate meal could provoke normal rise of blood glucose in the affected individuals, but could not evoke an y response after overnight fasting. Administration of raw-corn-starch could ma intain normoglycemia and improve the disease condition. Mutation analysis for pa tient 1 was normal. Patient 2 had a compound heterozygote: a C-to-T transition at nucleotide 1294 (come from father, 1294C>T, L 298 L) in exon 8 and a G-to- T transition at nucleotide 4747 (from mother, 4747G>T, E1450X) in exon 34. Patie nt 3 had a compound heterozygote: a C-to-T tra

关 键 词：糖原贮积症Ⅲ型 基因突变 糖原脱支酶 外显子 儿童 

分 类 号：R725.8[医药卫生—儿科]