Enzymatic characterization of four new mutations in the glucose-6 phosphatase (G6PC) gene which cause glycogen storage disease type 1a

N. BRUNI; F. RAJAS; S. MONTANO; F. CHEVALIER-PORST; I. MAIRE; G. MITHIEUX

doi:10.1046/j.1469-1809.1999.6320141.x

Abstract

Glycogen storage disease type 1a (GSD1a) is caused by mutations in the gene of glucose-6 phosphatase (G6PC), encoding the last enzyme of gluconeogenesis and glycogenolysis. To study the effect of mutations previously identified, but not yet enzymatically characterized, in French GSD1a patients, we used an in vitro expression system of the human glucose-6 phosphatase (hGlc6Pase) cDNA. Wild type hGlc6Pase expressed in COS-7 cells exhibited kinetic features comparable to microsomal Glc6Pase from normal human liver and kidney. Four new mutations inducing aminoacid changes in the coding sequence, e.g. W77R, A124T, G184E and L211P, were inserted into the Glc6Pase cDNA by site-directed mutagenesis, and studied after transient expression in COS-7 cells. All four mutations totally abolished Glc6Pase activity.

Crossref Citations

This article has been cited by the following publications. This list is generated based on data provided by Crossref.

Janecke, Andreas R. Mayatepek, Ertan and Utermann, Gerd 2001. Molecular Genetics of Type 1 Glycogen Storage Disease. Molecular Genetics and Metabolism, Vol. 73, Issue. 2, p. 117.

Shieh, Jeng-Jer Terzioglu, Mugen Hiraiwa, Hisayuki Marsh, Julia Pan, Chi-Jiunn Chen, Li-Yuan and Chou, Janice Yang 2002. The Molecular Basis of Glycogen Storage Disease Type 1a. Journal of Biological Chemistry, Vol. 277, Issue. 7, p. 5047.

Metón, Isidoro Caseras, Anna Fernández, Felipe and Baanante, Isabel V. 2004. Molecular cloning of hepatic glucose-6-phosphatase catalytic subunit from gilthead sea bream (Sparus aurata): response of its mRNA levels and glucokinase expression to refeeding and diet composition. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, Vol. 138, Issue. 2, p. 145.

Chou, Janice Y. and Mansfield, Brian C. 2008. Mutations in the glucose-6-phosphatase-α (G6PC) gene that cause type Ia glycogen storage disease. Human Mutation, Vol. 29, Issue. 7, p. 921.

NITTA, Yumiko SHIGEYOSHI, Yasufumi NAKAGATA, Naomi KANEKO, Takehito NITTA, Kohsaku HARADA, Toshihide ISHIZAKI, Fumiko and TOWNSEND, Jana 2009. Kinetics of Blood Glucose in Mice Carrying Hemizygous Pax6. Experimental Animals, Vol. 58, Issue. 2, p. 105.

Chou, Janice Y. Jun, Hyun Sik and Mansfield, Brian C. 2010. Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy. Nature Reviews Endocrinology, Vol. 6, Issue. 12, p. 676.

Mutel, Elodie Abdul-Wahed, Aya Ramamonjisoa, Nirilanto Stefanutti, Anne Houberdon, Isabelle Cavassila, Sophie Pilleul, Frank Beuf, Olivier Gautier-Stein, Amandine Penhoat, Armelle Mithieux, Gilles and Rajas, Fabienne 2011. Targeted deletion of liver glucose-6 phosphatase mimics glycogen storage disease type 1a including development of multiple adenomas. Journal of Hepatology, Vol. 54, Issue. 3, p. 529.

Rajas, F. Labrune, P. and Mithieux, G. 2013. Glycogen storage disease type 1 and diabetes: Learning by comparing and contrasting the two disorders. Diabetes & Metabolism, Vol. 39, Issue. 5, p. 377.

Clar, Julie Gri, Blandine Calderaro, Julien Birling, Marie-Christine Hérault, Yann Smit, G. Peter A. Mithieux, Gilles and Rajas, Fabienne 2014. Targeted deletion of kidney glucose-6 phosphatase leads to nephropathy. Kidney International, Vol. 86, Issue. 4, p. 747.

Clar, J. Mutel, E. Gri, B. Creneguy, A. Stefanutti, A. Gaillard, S. Ferry, N. Beuf, O. Mithieux, G. Nguyen, T. H. and Rajas, F. 2015. Hepatic lentiviral gene transfer prevents the long-term onset of hepatic tumours of glycogen storage disease type 1a in mice. Human Molecular Genetics, Vol. 24, Issue. 8, p. 2287.

Gjorgjieva, Monika Raffin, Margaux Duchampt, Adeline Perry, Ariane Stefanutti, Anne Brevet, Marie Tortereau, Antonin Dubourg, Laurence Hubert-Buron, Aurélie Mabille, Mylène Pelissou, Coralie Lassalle, Louis Labrune, Philippe Mithieux, Gilles and Rajas, Fabienne 2016. Progressive development of renal cysts in glycogen storage disease type I. Human Molecular Genetics, Vol. 25, Issue. 17, p. 3784.

Gjorgjieva, Monika Oosterveer, Maaike H. Mithieux, Gilles and Rajas, Fabienne 2016. Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment. Journal of Inborn Errors of Metabolism and Screening, Vol. 4, Issue. , p. 232640981667942.

Wang, Ting Xu, Dandan Fan, Qiming Rong, Weifeng Zheng, Jiewei Gao, Chen Li, Guoliang Zeng, Ni Guo, Tao Zeng, Lihai Wang, Fei Xiao, Chen Cai, Li Tang, Shangqing Deng, Xinlei Yin, Xiao Huang, Manqi Lu, Fengrong Hu, Qiansheng Chen, Wen Huang, Zhenlie and Wang, Qing 2017. 1,2-Dichloroethane impairs glucose and lipid homeostasis in the livers of NIH Swiss mice. Toxicology, Vol. 380, Issue. , p. 38.

Peeks, Fabian Steunenberg, Thomas A. H. de Boer, Foekje Rubio‐Gozalbo, M. Estela Williams, Monique Burghard, Rob Rajas, Fabienne Oosterveer, Maaike H. Weinstein, David A. and Derks, Terry G. J. 2017. Clinical and biochemical heterogeneity between patients with glycogen storage disease type IA: the added value of CUSUM for metabolic control. Journal of Inherited Metabolic Disease, Vol. 40, Issue. 5, p. 695.

Roseman, Daniel S. Khan, Tayeba Rajas, Fabienne Jun, Lucy S. Asrani, Kirtika H. Isaacs, Cleo Farelli, Jeremiah D. and Subramanian, Romesh R. 2018. G6PC mRNA Therapy Positively Regulates Fasting Blood Glucose and Decreases Liver Abnormalities in a Mouse Model of Glycogen Storage Disease 1a. Molecular Therapy, Vol. 26, Issue. 3, p. 814.

Gjorgjieva, Monika Monteillet, Laure Calderaro, Julien Mithieux, Gilles and Rajas, Fabienne 2018. Polycystic kidney features of the renal pathology in glycogen storage disease type I: possible evolution to renal neoplasia. Journal of Inherited Metabolic Disease, Vol. 41, Issue. 6, p. 955.

Gjorgjieva, Monika Calderaro, Julien Monteillet, Laure Silva, Marine Raffin, Margaux Brevet, Marie Romestaing, Caroline Roussel, Damien Zucman-Rossi, Jessica Mithieux, Gilles and Rajas, Fabienne 2018. Dietary exacerbation of metabolic stress leads to accelerated hepatic carcinogenesis in glycogen storage disease type Ia. Journal of Hepatology, Vol. 69, Issue. 5, p. 1074.

Jauze, Louisa Monteillet, Laure Mithieux, Gilles Rajas, Fabienne and Ronzitti, Giuseppe 2019. Challenges of Gene Therapy for the Treatment of Glycogen Storage Diseases Type I and Type III. Human Gene Therapy, Vol. 30, Issue. 10, p. 1263.

Rajas, Fabienne and Mithieux, Gilles 2019. Molecular Nutrition: Carbohydrates. p. 173.

Yavarow, Zollie A Kang, Hye-Ri Waskowicz, Lauren R Bay, Boon-Huat Young, Sarah P Yen, Paul M and Koeberl, Dwight D 2020. Fenofibrate rapidly decreases hepatic lipid and glycogen storage in neonatal mice with glycogen storage disease type Ia. Human Molecular Genetics, Vol. 29, Issue. 2, p. 286.

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Enzymatic characterization of four new mutations in the glucose-6 phosphatase (G6PC) gene which cause glycogen storage disease type 1a

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Enzymatic characterization of four new mutations in the glucose-6 phosphatase (G6PC) gene which cause glycogen storage disease type 1a

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