Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Glucokinase

Glucokinase is a key enzyme in regulation insulin secretion. Heterozygous inactivating mutations in GCK cause maturity-onset diabetes of the young type 2 (MODY2), whereas activating mutations result in hypoglycemia.

Epidemiology

MODY 2 diabetes is one of the most common types of MODY. About 10% of MODY in Germany is caused by glucokinase mutations. Mutations of glucokinase could be found wordlwide.

Gene Structure

The gen is located on chromosom 7 (7p15-p13). Its abbreviation is GCK. Size is about 45kb. It consists of 12 exons, 10 of them are translated.

Phenotype

Clinically mutation of this gene impresses as autosomal dominant MODY 2 Diabetes. Biochemically the picture is similar to type 2 diabetes but manifestation is early in life and there is no metabolic syndrome. The diabetes becomes apperent in situations of metabolic stress ie. in pregnancy or during medication with glucocorticoids.

Pathology

Glucokinase is an important enzyme in glucose metabolism. It is involved in degradation of glucose and produktion of ATP. Tis way the enzyme is regulates insulin secretion.

Test Strategy

Patients with family history and laboratory data suspect for MODY diabetes. Screening of family member in a known MODY family.

Interpretation

The detection of a mutation in this gene is a prerequisite for the diagnosis.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

MODY2 diabetes
GCK
Hyperinsulinemic hypoglycemia 3
GCK
Permanent neonatal diabetes mellitus
ABCC8
Developmental delay, epilepsy, and neonatal diabetes
KCNJ11
GCK
INS
KCNJ11
Phosphoribosylpyrophosphate synthetase superactivity
PRPS1
Wolcott-Rallison syndrome
EIF2AK3

References:

1.

None (2003) Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy.

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2.

Schnyder S et al. (2005) Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment.

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3.

Galán M et al. (2006) Effects of novel maturity-onset diabetes of the young (MODY)-associated mutations on glucokinase activity and protein stability.

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Update: Sept. 26, 2018