Nephrogenic Diabetes Insipidus (NDI) via the AQP2 Gene

Nephrogenic Diabetes Insipidus (NDI) is a kidney disorder characterized by polyuria (too much urine) and polydipsia (excessive thirst), which results from an insensitivity to vasopressin (also called antidiuretic hormone, ADH), a hormone that regulates the kidneys to retain water.

Inherited NDI patients usually display early onset (< 1 year old), poor feeding, failure to thrive, fever, short stature, and are prone to severe dehydration trigged by illness, hot environments and water depletion. Autosomal dominant NDI patients usually display milder symptoms and later onset compared to autosomal recessive NDI. Mutations in the AQP2 gene cause both autosomal dominant and autosomal recessive Nephrogenic Diabetes Insipidus (NDI) (OMIM# 125800), which accounts for 9% and 1% of inherited NDI respectively (Bichet. Advances in Chronic Kidney Disease 13(2):96-104, 2006; Schrier.Semin Nephrol 28(3):289-296, 2008 and Knoers. GeneReviews, 2012).

Inherited NDI can be caused by mutations in the AVPR2 and AQP2 genes. The AQP2 gene (OMIM# 107777) encodes an aquaporin-2 water channel protein in the renal collecting tubules, a key component of integral protein in the kidney's collecting duct. In response to AVP-AVPR2 coupled reaction, AQP2 protein translocates from intracellular to the apical plasma membrane to increase water permeability in renal tubules and to maintain water homeostasis. To date, more than 50 causative mutations have been identified; the majority of them are missense mutations (~85%) (Knoers, 2012).

AQP2 gene mutations can be detected by sequencing in about 10% of patients with clinical diagnosed nephrogenic diabetes insipidus (Knoers, 2012).

This test provides full coverage of all coding exons of the AQP2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).