Mutations in the glucose-6-phosphatase-α (G6PC) gene that cause type Ia glycogen storage disease
Open Access
- 30 April 2008
- journal article
- review article
- Published by Hindawi Limited in Human Mutation
- Vol. 29 (7), 921-930
- https://doi.org/10.1002/humu.20772
Abstract
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 three splicing mutations in the G6PC gene have been identified in more than 550 patients. Of these, 50 missense, two nonsense, and two 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. Hum Mutat 29(7), 921–930, 2008. Published 2008 Wiley‐Liss, Inc.Keywords
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