Scientific background:

Summary: The gene codes for the gamma subunit of the epithelial sodium channel, which regulates aldosteron dependend excretion of sodium in distal nephrons. Gain-of-function mutations result in Liddle syndrome whereas loss-of-function mutations lead to autosomal recessive Pseudohypoaldosternism 1.

Gene: The gene locus on chromosome 16 (16p12) is in the proximity to other components of the sodium channel. The 13 exons spread over 35kb. Only the last 12 of them become translated.

Pathology: The aldosteron-sensitive distal nephron consists of distal convoluted tubule (DCT), the connecting tubule (CNT), and the collecting duct (CD). This part of the nephron is characterized by the colocalization of the epithelial sodium channel (ENaC), the mineralocorticoid receptor, and the 11-beta hydroxysteroid dehydrogenase type 2. The gene codes for the gamma subunit of the channel. Gain-of-function mutations result in Liddle syndrome whereas loss-of-function mutations lead to Pseudohypoaldosteronism.

Clinical signs: Opposite phenotypes result depending on whether a gain- or loss-of-function mutation is present.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		20 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: 

Swift PA et al. (2004) The epithelial sodium channel in hypertension: genetic heterogeneity and implications for treatment with amiloride.
Capasso G et al. (2005) Channels, carriers, and pumps in the pathogenesis of sodium-sensitive hypertension.
Warnock DG et al. (2001) Liddle syndrome: genetics and mechanisms of Na+ channel defects.