Diabetes Insipidus: AQP2, AVP, AVPR2 Sequencing

Diagnostic Use

This test comprises analysis of three genes (AQP2, AVP, AVPR2) which are associated with different forms of diabetes insipidus (DI). This test is appropriate for patients for whom there is a clinical suspicion of DI.
Pathogenic variants in the AQP2, AVP, and AVPR2 genes affect water balance and can cause forms of DI, a disorder characterized by excessive production of dilute urine (polyuria) and excessive thirst (polydipsia):
AQP2 (Aquaporin-2) – Variants impair water reabsorption in the kidney’s collecting ducts, leading to autosomal nephrogenic diabetes insipidus (NDI). The kidneys cannot concentrate urine despite normal or elevated vasopressin levels.
AVP (Arginine Vasopressin) – Variants reduce or abolish production of vasopressin (antidiuretic hormone (ADH)) in the hypothalamus, causing autosomal central diabetes insipidus (CDI) (also referred to as hypophyseal diabetes insipidus), where the kidneys are normal but lack hormonal stimulation to retain water.
AVPR2 (Arginine Vasopressin Receptor 2) – Variants disrupt vasopressin binding/signaling in the collecting ducts, leading to X-linked nephrogenic diabetes insipidus, with a similar clinical presentation to AQP2-related NDI but due to receptor defects.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

NDI. CDI

Turnaround Time

4 weeks

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Additional Specimen Information

This test requires nucleated cells. Please do not centrifuge or freeze blood samples.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

This test requires nucleated cells. Please do not centrifuge or freeze blood samples.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Test Method

DNA is extracted from the peripheral blood sample, then analysed using a Twist Biosciences next generation sequencing (NGS) custom panel on an Illumina MiSeq instrument. The panel targets the following genes: AVP (NM_000490.5), AVPR2 (NM_000054.7), AQP2 (NM_000486.6). All coding regions and intron-exon boundaries are analysed to a minimum read depth of 30x. Copy number variants (CNVs) in the genes listed above are assessed by analysis of coverage depth data from the Twist NGS panel using a validated in-house algorithm.

Non-Funded Test Cost

$1051.37 (Exclusive of GST)

Billing Code

4566

Uncertainty of Measurement:
Next generation sequencing analysis has an analytical sensitivity and specificity of >99%. Note that the lower limit of variant detection of sequencing analysis is ~10%, this is important to consider in the case of mosaicism, mitochondrial, and somatic variation that is not expected to be present at 50% or 100%. This analysis will not detect variants located within intronic regions, except at the intron-exon boundaries.

Genomic DNA must be extracted from the specimen prior to testing. This incurs an additional charge (see GDNA). Laboratories may prefer to submit DNA for testing. Please provide a minimum of 5 micrograms of DNA at 20 nanograms/microlitre.

Contact Information

Enquiry Form