Hereditary calcium disorders: CASR, GNA11, AP2S1 sequencing

Diagnostic Use

Familial hypocalciuric hypercalcemia (FHH) is an inherited disorder that causes abnormally high levels of calcium in the blood (hypercalcemia) and low to moderate levels of calcium in urine (hypocalciuric). People with FHH usually do not have any symptoms and are often diagnosed by chance during routine bloodwork. Weakness, fatigue, issues with concentration, and excessive thirst (polydipsia) have been reported by some people with FHH. Rarely, people with this disorder experience inflammation of the pancreas (pancreatitis) or a build-up of calcium in the joints (chondrocalcinosis).
FHH is mainly classified into three different types depending on the genetic cause. FHH type 1 is the most common type of FHH and is caused by loss-of-function variants in the CASR gene. The protein made from the CASR gene, the calcium-sensing receptor, monitors and regulates the level of calcium in the blood. FHH type 2 is caused by changes in the GNA11 gene, and FHH type 3 is caused by changes in the AP2S1 gene. All three types of FHH are inherited in an autosomal dominant manner. In rare cases, FHH may be caused when a person's immune system mistakenly makes antibodies that attack the CaSR protein. The autoimmune form of FHH is not known to be caused by changes in a specific gene.
Gain-of-function variants in CASR result in Autosomal dominant hypocalcaemia (ADH) which manifests as low serum calcium.
This test analyses the CASR, GNA11, and AP2S1 genes.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

ADH
AP2S1
Calcium sensing receptor
CASR
FHH
GNA11
hypocalciuric hypercalcaemia

Turnaround Time

4 weeks

Test Code

7312

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

Pre-testing Requirements

Please alert the laboratory to any referrals requiring results in under 4 weeks.

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

Laboratories may prefer to submit DNA for testing. Please provide a minimum of 5 micrograms of DNA at 20 nanograms/microlitre.

This testing is not considered urgent and will be processed in batches. Please alert the laboratory to any referrals requiring results in under 4 weeks.

Test Method

Patient DNA is analysed using a Twist Biosciences next generation sequencing (NGS) custom panel on an Illumina MiSeq instrument. The panel targets the following genes that have been implicated in familial calcium disorders: CASR (NM_000388.4), GNA11 (NM_002067.5), AP2S1 (NM_004069.6).

Non-Funded Test Cost

$691.47 (Exclusive of GST)

Billing Code

9644

Uncertainty of Measurement:
The targeted NGS DNA sequencing method used in this 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.

Contact Information

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