Gitelman Syndrome via the SLC12A3 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4503 SLC12A3 81407 81407,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4503SLC12A381407 81407(x1), 81479(x1) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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

Gitelman syndrome (OMIM# 263800) is an inherited salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria (Simon et al. Nat Genet 12(1):24-30, 1996; Vargas-Poussou et al. J Am Soc Nephrol 22(4):693-703, 2011; Glaudemans et al. Eur J Hum Genet 20(3):263-70, 2012). It is the most common renal tubular disorder in Caucasians with a prevalence of 1 in 40,000. Gitelman syndrome has been mostly diagnosed during adulthood while some affected children have been observed from the age of 6. Common clinical features include transient periods of muscle weakness and tetany that may be accompanied by abdominal pains, vomiting and fever. Completely asymptomatic patients may only have chondrocalcinosis in adulthood.

Genetics

Gitelman syndrome is an autosomal recessive disorder mostly caused by loss-of-function mutations in the solute carrier family 12, member 3 (SLC12A3) gene (Simon et al., 1996; Vargas-Poussou et al., 2011; Glaudemans et al., 2012). SLC12A3 has 26 coding exons that encode the thiazide-sensitive NaCl cotransporter (NCC), which is the target for thiazide-type diuretics (a first-line pharmacological treatment of hypertension). Genetic defects of SLC12A3 occur throughout the whole gene and include missense (59%), nonsense (5%), splicing site mutations (13%), small deletion/insertions (17%) and large deletions/duplications (6%) (Human Gene Mutation Database; Vargas-Poussou et al., 2011). Nearly half of patients who only had a single mutation detected by direct sequencing have been found to have a large deletion or duplication at the second allele via exon-level copy number testing (Vargas-Poussou et al., 2011). Notably, two recurrent deep intronic splicing mutations c.1670-191C>T and c.2548+253C>T have been reported with an indication of mutational hot spots rather than a founder effect (Nozu et al. Pediatr Res 66(5):590-593, 2009; Lo et al. Clin J Am Soc Nephrol 6(3):630-639, 2011). A minority of the Gitelman syndrome phenotype are caused by mutations in the CLCNKB gene, which is a major causative gene for Bartter syndrome (Simon et al. Nat Genet 17(2):171-178, 1997; Vargas-Poussou et al., 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

In a large cohort of 448 patients in whom Gitelman syndrome was suspected, direct sequencing identified homozygous and compound heterozygous SLC12A3 mutations in 70% of patients; only one mutated allele was identified in 18% of patients (Vargas-Poussou et al. J Am Soc Nephrol 22(4):693-703, 2011). In another study of 163 patients with a clinical suspicion of Gitelman syndrome, direct sequencing identified homozygous (39/163) and compound heterozygous (99/163) SLC12A3 mutations in 138 (~ 85%) of patients; only one mutated allele was identified in the remaining 25 patients (Glaudemans et al. Eur J Hum Genet 20(3):263-270, 2012).

Testing Strategy

This test provides full coverage of all coding exons of the SLC12A3 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

This test also includes targeted testing of two deep intronic splicing mutations c.1670-191C>T and c.2548+253C>T (Nozu et al., 2009; Lo et al., 2011).

Indications for Test

Candidates for this test are patients with Gitelman syndrome. Testing is also indicated for family members of patients who have known SLC12A3 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC12A3.

Gene

Official Gene Symbol OMIM ID
SLC12A3 600968
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Familial Hypokalemia-Hypomagnesemia AR 263800

Related Test

Name
Hypomagnesemia Panel

Citations

  • Glaudemans, B. et al. (2012). PubMed ID: 22009145
  • Human Gene Mutation Database (Bio-base).
  • Lo, Y. et al. (2011). PubMed ID: 21051746
  • Nozu, K. et al. (2009). PubMed ID: 19668106
  • Simon, D. et al. (1996). PubMed ID: 8528245
  • Simon, D. et al. (1997). PubMed ID: 9326936
  • Vargas-Poussou, R. et al. (2011). PubMed ID: 21415153

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

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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: $
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