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Hypophosphatemic Nephrolithiasis/Osteoporosis-2 (NPHLOP2) via the NHERF1/SLC9A3R1 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
8659 NHERF1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8659NHERF181479 81479,81479 $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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Nephrolithiasis is a clinical condition in which urinary supersaturation leads to stone formation in the urinary system (the lumen of the collecting system, ureter, and bladder) (Braun et al. 2016; Halbritter et al. 2015; Gee et al. 2016). Patients with kidney stones may have no symptoms or may present with flank pain, gross or microscopic hematuria, obstruction of one or both kidneys, and urinary infections. It affects 10%-15% of adults in their lifetime. SLC9A3R1-associated nephrolithiasis presents with hypophosphatemia and decreased renal phosphate resorption characterized by significantly decreased tubular maximum for phosphate resorption per glomerular filtration rate (TmP/GFR) (Karim et al. 2008). Some patients may also have a spinal deformity and decreased bone mineral density (BMD).

Genetics

SLC9A3R1-associated nephrolithiasis is an autosomal dominant disorder (Karim et al. 2008; Halbritter et al. 2015). The NHERF1/SLC9A3R1 gene (six coding exons) encodes sodium-hydrogen exchanger regulatory factor 1 (NHERF1), which controls renal phosphate transport. To date, documented genetic defects of NHERF1 include both missense and truncating variants (Human Gene Mutation Database). Large deletions/duplications have not been reported to date.

Clinical Sensitivity - Sequencing with CNV PGxome

In the original report of SLC9A3R1-associated nephrolithiasis, 4 of 92 (4.3%) unrelated patients with either nephrolithiasis or bone demineralization were found to have a heterozygous pathogenic NHERF1 variant (Karim et al. 2008).

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). Two families (0.75%) were found to have a heterozygous pathogenic NHERF1 variant.

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 genes known nephrolithiasis/nephrocalcinosis genes, leading to a molecular diagnosis in 16.8% (24 of 143) (Braun et al. 2016). One individual (0.7%) was found to have a heterozygous pathogenic NHERF1 variant.

Testing Strategy

This test provides full coverage of all coding exons of the NHERF1 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 hypophosphatemic nephrolithiasis/osteoporosis-2 (NPHLOP2). Testing is also indicated for family members of patients who have known pathogenic variants in the NHERF1 gene.

Gene

Official Gene Symbol OMIM ID
NHERF1 604990
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Nephrolithiasis/Osteoporosis, Hypophosphatemic, 2 AD 612287

Related Test

Name
Nephrolithiasis and Nephrocalcinosis Panel

Citations

  • Braun D.A. et al. 2016. Clinical Journal of the American Society of Nephrology. 11: 664-72. PubMed ID: 26787776
  • Gee H.Y. et al. 2016. American Journal of Human Genetics. 98: 1228-34. PubMed ID: 27210743
  • Halbritter et al. 2015. PubMed ID: 25296721
  • Human Gene Mutation Database (Bio-base).
  • Karim Z. et al. 2008. The New England Journal of Medicine. 359: 1128-35. PubMed ID: 18784102

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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