Scientific background:

Summary: The gene encoding an important renal potassium channel causes, when mutated, autosomal recessive antenatal Bartter syndrome type 2.

Molecular anatomy: The gene is expressed in epithelial cells of the thick ascending limb of the loop of Henle. The mature protein, a potassium channel, resides in the apical membrane.

Pathophysiology: This inwardly rectifying potassium channel forms a functional unit with the sodium-potassium-chloride cotransporter. The cotransporter moves sodium and potassium, one of each ion, and two chloride from lumen into cell. The excess of sodium and chroride is removed basolateral transpoters, the sodium-potassium ATPase and a chloride channel. The excess potassium however is recycled back into the lumen by an inwardly rectifying potassium channel. Hence this channel keeps the system of net sodium chlorid reabsorption running.
   WNK1 and WNK2, the genes involved in pseudohypoaldosteronism type 2, interact with intersectin-1 (ITSN1), an endocytic scaffold protein, thereby stimulating the potassium channel (ROMK) endocytosis. Hence, These genes play an important role in regulating channel function.

Clinical signs: As the potassium channel (ROMK) and the sodium-potassium-chloride cotransporter (NKCC2) form a functional unit, dysfuntion of either component causes the same clinical picture of autosomal recessive antenatal Bartter syndrome.

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		little
		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: 

Simon DB et al. (1996) Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK.
Schwalbe RA et al. (1998) Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment.
et al. (1997) Mutations in the gene encoding the inwardly-rectifying renal potassium channel, ROMK, cause the antenatal variant of Bartter syndrome: evidence for genetic heterogeneity. International Collaborative Study Group for Bartter-like Syndromes.
He G et al. (2007) Intersectin links WNK kinases to endocytosis of ROMK1.