Hypophosphatemic Rickets with Hypercalciuria via the SLC34A3 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
11675 SLC34A3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11675SLC34A381479 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.

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

Clinical Features and Genetics

Clinical Features

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive disorder characterized by hypophosphatemia (secondary to renal phosphate wasting), hypercalciuria, rickets, limb deformities, muscle weakness, and bone pain (Bergwitz et al. 2006. PubMed ID: 16358214; Lorenz-Depiereux et al. 2006. PubMed ID: 16358215). Compared with other types of hypophosphatemic rickets, patients with HHRH present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption. Age of onset is in infancy or early childhood. Of note, familial carriers who are heterozygous for a single pathogenic SLC34A3 variant frequently showed hypercalciuria with mild hypophosphatemia and/or increased serum 1,25-dihydroxyvitamin D3, but no bone disease or rickets, suggesting a milder phenotype of autosomal dominant inheritance in some patients (Bergwitz et al. 2006. PubMed ID: 16358214; Dasgupta et al. 2014. PubMed ID: 24700880).

Genetics

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive disorder caused by defects in the SLC34A3 gene (Bergwitz et al. 2006. PubMed ID: 16358214; Lorenz-Depiereux et al. 2006. PubMed ID: 16358215). As mentioned above, however, familial carriers frequently show a milder phenotype. The SLC34A3 gene (12 coding exons) encodes the renal sodium-phosphate cotransporter NaPi-IIc, which plays a key role in the regulation of phosphate homeostasis. To date, documented genetic defects of SLC34A3 include both missense and truncating variants (splicing variants and small indels, mostly frameshift) (Human Gene Mutation Database). Large deletions have been reported, but appear to be rare.

Clinical Sensitivity - Sequencing with CNV PGxome

The pathogenic variant detection rate in the SLC34A3 gene in a large cohort of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is unavailable because each individual study only reported a single family or limited number of cases (Human Gene Mutation Database).

In an international cohort comprising 272 genetically unresolved individuals (106 children and 166 adults) from 268 families with nephrolithiasis (n=256) or isolated nephrocalcinosis (n=16), Halbritter et al. detected likely (or suspected) causative variants in 14 of 30 analyzed genes, leading to a molecular diagnosis in 14.9% (40 of 268) of all cases (Halbritter et al. 2015. PubMed ID: 25296721). One family (0.37%) was found to have two novel heterozygous missense variants in SLC34A3.

In another international pediatric cohort comprising 143 individuals under 18 years of age, with nephrolithiasis (n=123) or isolated nephrocalcinosis (n=20), Braun et al. detected likely (or suspected) causative variants in 14 of the same set of 30 known nephrolithiasis/nephrocalcinosis genes, leading to a molecular diagnosis in 16.8% (24 of 143) of affected individuals (Braun et al. 2016. PubMed ID: 26787776). No pathogenic variants were found in SLC34A3.

Large deletions have been reported involving SLC34A3, but appear to be rare (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the SLC34A3 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 are patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Testing is also indicated for family members of patients who have known pathogenic variants in the SLC34A3 gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC34A3.

Gene

Official Gene Symbol OMIM ID
SLC34A3 609826
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Autosomal Recessive Hypophosphatemic Bone Disease AR 241530

Citations

  • Bergwitz et al. 2006. PubMed ID: 16358214
  • Braun et al. 2016. PubMed ID: 26787776
  • Dasgupta et al. 2014. PubMed ID: 24700880
  • Halbritter et al. 2015. PubMed ID: 25296721
  • Human Gene Mutation Database (Bio-base).
  • Lorenz-Depiereux et al. 2006. PubMed ID: 16358215

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

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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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