Scientific background:

Summary: 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.

Gene: 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.

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.

Clinical signs: 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.

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.

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

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

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		medium
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Multiplex Ligation-Dependent Probe Amplification
		Turn-around time		25 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

Gloyn AL et al. (2003) Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy.
Galán M et al. (2006) Effects of novel maturity-onset diabetes of the young (MODY)-associated mutations on glucokinase activity and protein stability.
Schnyder S et al. (2005) Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment.