Scientific background:

Summary: The gene SLC12A1 encoding a sodium-potassium-chloride cotransporter (NKCC2) is expressed in the thick ascending limb of the loop of Henle. Inactivating mutations are known to cause autosomal recessive antenatal Bartter syndrome type 1.

Gene: The SLC12A1 gene belongs to a superfamily of electroneutral cotransporters, which include another basolateral sodium-potassium-chloride cotransporter, a sodium-chloride cotransporter, and four potassium-chloride cotransporters. These genes are highly homologeous.
   The gene is translated into six different isoforms. These isoforms can be formed by anycombination of tree differens exon four cassettes and two alternative C-termini. These isoforms behave distinctively, which allows to fine tune the transport capacity in accordance to the increasingly dilute urine.

Molecular anatomy: The sodium-potassium-chloride cotransporter (NKCC2) is an apical membrane protein of the thick ascending limb of Henle. The six isoforms exhibit different kinetic behaviour. Accompanying the progressive dilution of the urine, these isoforms diplay a distinct axial distribution.

Clinical signs: Mutations of the SLC12A1 gene ensuing inactivation of the sodium-potassium-chloride cotransporter increase water and salt excretion which becomes noticable before birth, by polyhydramnion. The disease is called antenatal Bartter-syndrome 1.  » » » 

Epidemiology: Although exact data are not available, mutation in this gene are thought to occur 1 in 50,000-100,000 newborn.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		10 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		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: 

Starremans PG et al. (2003) Dimeric architecture of the human bumetanide-sensitive Na-K-Cl Co-transporter.