Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease.
Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease.
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葡萄糖-6-磷酸酶-alpha（G6PC）基因的突变，导致IA型糖原储存疾病。
DOI：
10.1002/humu.20772
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发表时间：
2008-07
期刊：
影响因子：
3.9
通讯作者：
Mansfield, Brian C.
中科院分区：
文献类型：
--
作者：
Chou, Janice Y.;Mansfield, Brian C.
葡萄糖-6-磷酸酶-α（Glucose-6-phosphatase-α，G6 PC）是维持葡萄糖稳态的关键酶，在葡萄糖生成和糖原分解的最后一步催化葡萄糖-6-磷酸水解为葡萄糖和磷酸。位于染色体17 q21上的G6 PC基因的突变导致Ia型糖原累积病（GSD-Ia），一种常染色体隐性代谢紊乱。GSD-Ia患者表现出葡萄糖稳态失调，其特征为空腹低血糖、肝肿大、肾肿大、高脂血症、高尿酸血症、乳酸血症和生长迟缓。G6 PC是一种高度疏水的糖蛋白，锚定在内质网的膜上，活性中心面向内腔。迄今为止，在550多名患者中已发现G6 PC基因中的54个错义突变、10个无义突变、17个插入/缺失突变和3个剪接突变。其中，50个错义突变，2个无义突变和2个插入/缺失突变已在功能上表征其对酶活性和稳定性的影响。虽然GSD-Ia在任何种族群体中并不更普遍，但已描述了高加索人、东方人和犹太人群体特有的突变。尽管如此，GSD-Ia患者表现出表型异质性，并不存在严格的基因型-表型关系。
Glucose-6-phosphatase-α (G6PC) is a key enzyme in glucose homeostasis that catalyzes the hydrolysis of glucose-6-phosphate to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis. Mutations in the G6PC gene, located on chromosome 17q21, result in glycogen storage disease type Ia (GSD-Ia), an autosomal recessive metabolic disorder. GSD-Ia patients manifest a disturbed glucose homeostasis, characterized by fasting hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, lactic acidemia, and growth retardation. G6PC is a highly hydrophobic glycoprotein, anchored in the membrane of the endoplasmic reticulum with the active center facing into the lumen. To date, 54 missense, 10 nonsense, 17 insertion/deletion, and 3 splicing mutations in the G6PC gene have been identified in more than 550 patients. Of these, 50 missense, 2 nonsense, and 2 insertion/deletion mutations have been functionally characterized for their effects on enzymatic activity and stability. While GSD-Ia is not more prevalent in any ethnic group, mutations unique to Caucasian, oriental, and Jewish populations have been described. Despite this, GSD-Ia patients exhibit phenotypic heterogeneity and a stringent genotype-phenotype relationship does not exist.
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