Scientific background:

Summary: Mutations in the vasopressin receptor 2 gene are responsible for x-linked nephrogenic diabetes insipidus.

Gene: The AVPR2 gene encoding the arginine vasopressin receptor 2 is located on the X chromosome (Xq28). It spans about 2.2kb and consists of 3 exons.

Molecular anatomy: The ADH receptor (V2) was predominantly investigated in kidney's collecting duct cells, where it regulates vasopressin dependent urine concentration. Physiological investigations in patients with or without known defects of vasopressin receptor 2 (V2) suggest that this receptor plays a role in secretion of coagulation factors and vasodilatation and that cells other than collecting duct epithelia carry this receptor.

Pathophysiology: Several different physiological functions are regulated by this receptor among them water excretion, secretion of coagulation factors and vasodilatation.

Clinical signs: Mutations in the AVPR2 gene lead to nephrogenic diabetes insipidus transmitted in an x-lined fashion. This means in each affected family males show a marked polyuria while females are predominantly asymptomatic. They may become symptomatic however during pregnancy when the placenta releases vasopressinase which reduces the plasma vasopressin level.

Methodology:

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

Gade W et al. (2006) A brief survey of aquaporins and their implications for renal physiology.
Fujiwara TM et al. (2005) Molecular biology of hereditary diabetes insipidus.
Noda Y et al. (2005) Trafficking mechanism of water channel aquaporin-2.
Nguyen MK et al. (2003) Molecular pathogenesis of nephrogenic diabetes insipidus.