|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We have identified two novel GCK-CHI mutations in young patients and investigated their pathogenicity by enzyme kinetic analysis, which expanded the spectrum of this rare disease.
|
31094068 |
2019 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion and hypoglycemia.
|
29044608 |
2018 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mechanistic Origins of Enzyme Activation in Human Glucokinase Variants Associated with Congenital Hyperinsulinism.
|
29425029 |
2018 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Here, we validated and improved their specificity by performing a comprehensive bioinformatics analysis combined with experimental and clinical data on a model of glucokinase (GCK): 8835 putative variations, including 515 disease-associated variations from 1596 families with diagnoses of monogenic diabetes (GCK-MODY) or persistent hyperinsulinemic hypoglycemia of infancy (PHHI), and 126 variations with available or newly reported (19 variations) data on enzyme kinetics.
|
28842611 |
2017 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Biochemical and structural analysis of this loop variant and GCK variants associated with hyperinsulinemic hypoglycemia reveal two distinct mechanisms of enzyme activation.
|
26283387 |
2015 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Glutamate dehydrogenase-CHI is the second most common cause of CHI, while HNF4A and GCK are rare types of CHI in Chinese patients.
|
25008049 |
2014 |
|
Congenital Hyperinsulinism
|
0.500 |
Biomarker
|
disease |
BEFREE |
Glucokinase (GCK) acts as a glucose sensor and stimulates the release of insulin from pancreatic β-cells and any GCK gene mutations can lead to different forms of diabetes, such as GCK-monogenic diabetes of the young type 2 (MODY2), permanent neonatal diabetes and congenital hyperinsulinism.
|
23890519 |
2013 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We report two novel GCK HH mutations (V389L and T103S) at residues where MODY mutations also occur (V389D and T103I).
|
21454522 |
2011 |
|
Congenital Hyperinsulinism
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Activity and protein expression of GK-MODY and persistent hyperinsulinemic hypoglycemia of infancy (PHHI) mutants were studied in β-cell (MIN6) and non-β-cell (H4IIE) models.
|
22028181 |
2011 |
|
Congenital Hyperinsulinism
|
0.500 |
Biomarker
|
disease |
BEFREE |
Diazoxide is the first-line drug for the rare forms of CHI for long-term treatment but is not entirely effective in some of these rarer defects (GCK, MCT1).
|
21186003 |
2011 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.
|
19790256 |
2009 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Dominant forms of CHI are due to inactivating mutations in ABCC8 and KCNJ11, and activating mutations in GLUD1 (encoding glutamate dehydrogenase) and GCK (encoding glucokinase).
|
19254908 |
2009 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We describe the discovery of 11 new activating mutations in the human glk gene associated with the disease persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
|
19146401 |
2009 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
LHGDN |
In the combined Danish and Norwegian cohort, the prevalence of GCK-CHI was estimated to be 1.2% (2/167, 95% confidence interval (CI) 0-2.8%) of all the CHI patients.
|
18450771 |
2008 |
|
Congenital Hyperinsulinism
|
0.500 |
Biomarker
|
disease |
BEFREE |
In the combined Danish and Norwegian cohort, the prevalence of GCK-CHI was estimated to be 1.2% (2/167, 95% confidence interval (CI) 0-2.8%) of all the CHI patients.
|
18450771 |
2008 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Congenital hyperinsulinism is associated with mutations of SUR-1 and Kir6.2, glucokinase, glutamate dehydrogenase, short-chain 3-hydroxyacyl-CoA dehydrogenase, and ectopic expression on beta-cell plasma membrane of SLC16A1.
|
18156285 |
2008 |
|
Congenital Hyperinsulinism
|
0.500 |
Biomarker
|
disease |
BEFREE |
GCK-PHHI patients have regulated insulin secretion and can usually be treated with diazoxide.
|
17976205 |
2007 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
In contrast to focal islet-cell hyperplasia, always sporadic to our knowledge, diffuse hyperinsulinism is a heterogeneous disorder involving several genes, various mechanisms of pathogenic mutations and different transmissions: (i) channelopathy involving the genes encoding the sulphonylurea receptor (SUR1) or the inward-rectifying potassium channel (Kir6.2) in recessively inherited HI or more rarely dominantly inherited HI; (ii) metabolic disorders implicating the short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) enzyme inrecessively inherited HI, the glucokinase gene (GK), the glutamate dehydrogenase gene (GLUD1) when hyperammonemia is associated, dominant exercise-induced HI with still-unknown mechanism, and more recently the human insulin receptor gene in dominantly inherited hyperinsulinism.
|
15868462 |
2005 |
|
Congenital Hyperinsulinism
|
0.500 |
Biomarker
|
disease |
CTD_human |
Heterozygous inactivating mutations in the glucokinase gene (GCK) cause a mild form of diabetes (maturity-onset diabetes of the young [MODY]2), and activating mutations have been associated with a mild form of familial hyperinsulinemic hypoglycemia.
|
15277402 |
2004 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Heterozygous inactivating mutations in the glucokinase gene (GCK) cause a mild form of diabetes (maturity-onset diabetes of the young [MODY]2), and activating mutations have been associated with a mild form of familial hyperinsulinemic hypoglycemia.
|
15277402 |
2004 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Others cases of CHI are due to rare mutations in the beta-cell enzymes glucokinase (only one family described) and glutamate dehydrogenase in hyperammonaemia-associated hyperinsulinism.
|
12566718 |
2003 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy.
|
14517946 |
2003 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Biochemical genetic studies have characterized many activating and inactivating GK mutants that have been discovered in patients with hyperinsulinemic hypoglycemia or diabetes, all inherited as autosomal dominant traits.
|
12475782 |
2002 |
|
Congenital Hyperinsulinism
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
In this study, a second case of hyperinsulinemic hypoglycemia due to activation of glucokinase is reported.
|
11916951 |
2002 |
|
Congenital Hyperinsulinism
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
An activating mutation in the "glucose sensor" glucokinase has recently been reported in one family with diazoxide-responsive autosomal dominant hyperinsulinemic hypoglycemia.
|
10805170 |
2000 |