DNA icon

Hypercalcemic and Hypocalcemic Disorders via the GNA11 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11359 GNA11 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11359GNA1181479 81479(x2) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Familial hypocalciuric hypercalcemia (FHH) is a heritable disorder of mineral homeostasis characterized by lifelong elevation of serum calcium concentrations. FHH patients are usually asymptomatic and the disorder is generally considered benign. Clinical features of FHH include hypermagnesemia and low urinary calcium excretion. FHH patients have normal or mildly elevated circulating parathyroid hormone (PTH) level. In uncommon symptomatic cases, some adult patients have chondrocalcinosis and pancreatitis while some children may develop neonatal severe hyperparathyroidism (NSHPT). The age of FHH onset is mostly in infancy, but severe FHH can present in either childhood or early adulthood. FHH is a genetically heterogeneous disorder and consists of three variants: FHH1, FHH2 and FHH3. FHH2 is caused by dominant inactivating GNA11 mutations.

Autosomal dominant hypocalcemia (ADH) is characterized by mild to moderate hypocalcemia. ADH patients are generally asymptomatic, but some patients may have neuromuscular symptoms such as paresthesia, carpopedal spasm and seizures. Other common features of ADH include hyperphosphatemia, hypomagnesemia and relative hypercalciuria. ADH consists of two variants: ADH1 and ADH2. ADH2 is caused by dominant activating GNA11 mutations (Mannstadt et al. 2013; Nesbit et al. 2013).

Genetics

GNA11 has 7 coding exons that encode the subunit alpha-11 of a G-protein member. Patients with defects in this protein exhibit decreased or increased sensitivity, respectively, to changes in extracellular calcium concentrations. Genetic defects found so far in the GNA11 gene include missense mutations and small deletions. No large deletions or insertions have been reported in GNA11 for hypercalcemia or hypocalcemia (Human Gene Mutation Database).

Familial hypocalciuric hypercalcemia type 2 (FHH2) is an autosomal dominant disorder caused by inactivating GNA11 mutations (Mannstadt et al. 2013; Nesbit et al. 2013). The other two FHH-causative genes are CASR (FHH1) and AP2S1 (FHH3) (Nesbit et al. 2013; Hannan et al. 2013). CASR mutations were detected in around 65% of FHH patients.

Autosomal dominant hypocalcemia type 2 is an autosomal dominant disorder caused by activating GNA11 mutations (Mannstadt et al. 2013; Nesbit et al. 2013). The other known ADH-causative gene is CASR (Hannan et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

Detection rate of pathogenic variants in the GNA11 gene in a large cohort of patients with familial hypocalciuric hypercalcemia type 2 or autosomal dominant hypocalcemia type 2 is unknown in the literature because documented GNA11 pathogenic variants have been reported only in limited cases.

Testing Strategy

This test provides full coverage of all coding exons of the GNA11 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).

Indications for Test

Candidates for this test can be patients with familial hypocalciuric hypercalcemia type 2 or autosomal dominant hypocalcemia type 2. Testing is also indicated for family members of patients who have known GNA11 mutations.

Gene

Official Gene Symbol OMIM ID
GNA11 139313
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Hannan FM, Thakker RV. 2013. Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte and water metabolism. Best Pract. Res. Clin. Endocrinol. Metab. 27: 359–371. PubMed ID: 23856265
  • Human Gene Mutation Database (Bio-base).
  • Mannstadt M, Harris M, Bravenboer B, Chitturi S, Dreijerink KMA, Lambright DG, Lim ET, Daly MJ, Gabriel S, Jüppner H. 2013. Germline mutations affecting Gα11 in hypoparathyroidism. N. Engl. J. Med. 368: 2532–2534. PubMed ID: 23802536
  • Nesbit MA, Hannan FM, Howles SA, Babinsky VN, Head RA, Cranston T, Rust N, Hobbs MR, Heath H 3rd, Thakker RV. 2013. Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia. N. Engl. J. Med. 368: 2476–2486. PubMed ID: 23802516
  • Nesbit MA, Hannan FM, Howles SA, Reed AAC, Cranston T, Thakker CE, Gregory L, Rimmer AJ, Rust N, Graham U, Morrison PJ, Hunter SJ, Whyte MP, McVean G, Buck D, Thakker RV. 2013. Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. Nat. Genet. 45: 93–97.  PubMed ID: 23222959

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
×
Copy Text to Clipboard
×