Scientific background:

Summary: The gene ABCC8 encodes the sulfonylurea receptor a component that regulates the potassium channel in pancreatic beta cells. Loss-of-function mutations and inhibition of the protein result in stimulation of the insulin secretion. Familial hyperinsulinemic hypoglycemia is an autosomal recessive and less commonly dominant disorder. Gain-of-function mutations result in permanent or transient neonatal diabetes mellitus which is an autosomal recessive or dominant disorder.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		large
		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		large
		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: 

Thomas PM et al. (1995) Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy.
Nestorowicz A et al. (1996) Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.
Glaser B et al. (1999) Intragenic single nucleotide polymorphism haplotype analysis of SUR1 mutations in familial hyperinsulinism.
Thomas PM et al. (1996) Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.
Dunne MJ et al. (1997) Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor.
Verkarre V et al. (1998) Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.
Huopio H et al. (2000) Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1.
Huopio H et al. (2003) A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1.
Magge SN et al. (2004) Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor.
Otonkoski T et al. (1999) A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.
Thornton PS et al. (1998) Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant.
Thornton PS et al. (2003) Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor.
Tornovsky S et al. (2004) Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity.
Proks P et al. (2006) A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.
Babenko AP et al. (2006) Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.
Ellard S et al. (2007) Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.