Diabetes Insipidus: AQP2, AVP, AVPR2 Sequencing

Diagnostic Use

Nephrogenic diabetes insipidus (NDI) is an early onset disorder (infancy/neonatal) of fluid imbalance, which is characterized by the inability to concentrate the urine, which results in polyuria (excessive urine production) and polydipsia (excessive thirst). The disease results from the failure of the renal tubules to respond to antidiuretic hormone. Short stature and secondary dilatation of the ureters and bladder from the high urine volume is common in untreated individuals. Acute hypernatremic dehydration after birth may cause neurological sequelae. The prevalence of NDI is estimated at 1-2:1,000,000 worldwide. When NDI results from mutations in the AVPR2 gene, the condition has an X-linked recessive pattern of inheritance, and makes up about 90 percent of all cases. Some females who carry a single mutated copy of the AVPR2 gene have features of NDI. NDI caused by mutations in the AQP2 gene, can have either an autosomal recessive or an autosomal dominant pattern of inheritance. Both of these genes provide instructions for making proteins that help determine how much water is excreted in urine.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

NDI

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

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