Scientific background:

Summary: Mutations of this gene are responsible for autosomal recessive and dominant nephrogenic diabetes insipidus.

Gene: The gene encoding the water channel aquaporin 2 is located on chromosome 12 (12q13) and spans about 8.1kb. It consists of 4 exons, all of them translated.

Molecular anatomy: This water channel aquaporin 2 shows the same distribution as the arginine vasopressin receptor. In kidney's collecting duct both molecules regulate ADH dependent water excretion.

Pathophysiology: Aquaporin 2 trafficking from cytoplasmic vesicles to the apical membrane is stimulated by cGMP. Phosphorylation of serin at 256 is essential. Signal transduction can be initiated by arginine vasopressin (ADH), atrial natriuretic factor (ANP) or nitric oxide (NO).

Clinical signs: The phenotype of AQP2 mutations includes nephrogenic diabetes insipidus either autosomal recessive or dominant.

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.