Nephrolithiasis and Nephrocalcinosis Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10395 ADCY10 81479,81479 Order Options and Pricing
AGXT 81479,81479
APRT 81479,81479
ATP6V0A4 81479,81479
ATP6V1B1 81479,81479
CA2 81479,81479
CASR 81405,81479
CLCN5 81479,81479
CLDN16 81479,81479
CLDN19 81479,81479
CYP24A1 81479,81479
FAM20A 81479,81479
GRHPR 81479,81479
HNF4A 81406,81479
HOGA1 81479,81479
HPRT1 81479,81479
KCNJ1 81404,81479
OCRL 81479,81479
SLC12A1 81407,81479
SLC22A12 81479,81479
SLC26A1 81479,81479
SLC2A9 81479,81479
SLC34A1 81479,81479
SLC34A3 81479,81479
SLC3A1 81479,81479
SLC4A1 81479,81479
SLC7A9 81479,81479
SLC9A3R1 81479,81479
VDR 81479,81479
XDH 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10395Genes x (30)81479 81404, 81405, 81406, 81407, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

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.

Nephrocalcinosis is a clinical-pathological entity referring to the diffuse, radiologically demonstrable deposition of calcium salts within the kidney parenchyma (Piccoli et al. 2016; Hsi et al. 2015).

Genetics

The formation of kidney stones is a multifactorial process involving an interaction of environmental, dietary, and genetic factors. Therefore, it is a group of highly genetically heterogeneous diseases. To date, at least 30 genes have been linked to a monogenic form of nephrolithiasis or nephrocalcinosis in autosomal-dominant, autosomal-recessive, or X-linked inheritance as listed below (Braun et al. 2016; Halbritter et al. 2015; Gee et al. 2016). The spectrum of pathogenic variants throughout these genes includes all types of changes.

Autosomal dominant: ADCY10 (hypercalciuria, calcium oxalate nephrolithiasis), SLC9A3R1 (nephrolithiasis due to impaired renal phosphate reabsorption), CASR (hypocalcemia), HNF4A (MODY, Fanconi syndrome and nephrocalcinosis)

Autosomal dominant or recessive: SLC3A1 (cystinuria, type A), SLC7A9 (cystinuria, type B), SLC22A12 (renal hypouricemia, type 1), SLC2A9 (renal hypouricemia, type 2), SLC34A1 (hypophosphataemic nephrolithiasis/osteoporosis; hypercalcemia), VDR (vitamin D resistant rickets or osteoporosis), SLC4A1 (distal renal tubular acidosis)

Autosomal recessive: ATP6V0A4 (distal renal tubular acidosis), ATP6V1B1 (distal renal tubular acidosis with deafness), CA2 (distal renal tubular acidosis with osteopetrosis), CLDN16 (renal hypomagnesemia 3), CLDN19 (renal hypomagnesemia 5 with ocular abnormalities), AGXT (primary hyperoxaluria, type 1), GRHPR (primary hyperoxaluria, type 2), HOGA1 (primary hyperoxaluria, type 3), CYP24A1 (infantile hypercalcaemia), SLC34A3 (hypophosphatemic rickets with hypercalciuria), APRT (adenine phosphoribosyltransferase deficiency), FAM20A (Enamel-Renal syndrome, amelogenesis imperfecta and nephrocalcinosis), SLC12A1 (Bartter syndrome, type 2), KCNJ1 (Bartter syndrome, type 2), XDH (xanthinuria), SLC26A1 (calcium oxalate nephrolithiasis)

X-Linked recessive: CLCN5 (Dent disease 1), OCRL (Lowe syndrome/Dent disease 2), HPRT1 (Lesch-Nyhan syndrome)

See individual gene test descriptions for more information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

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). The mutation detection rates of these 14 individual genes can be found at the Halbritter et al. report.

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). The mutation detection rates of these 14 individual genes can be found at the Braun et al. report.

Our current panel includes 29 of the 30 genes described above. The CLCNKB gene (Bartter syndrome, type 3) is excluded due to next generation sequencing technology’s limitations with highly similar sequences. No plausible pathogenic variants were found in CLCNKB in either the Halbritter et al. or Braun et al. study. Therefore, the overall mutation detection rate thorough our current panel is expected to be nearly the same as that of the two studies mentioned above for nephrolithiasis or nephrocalcinosis patients.

Our current panel also includes the very recently identified nephrolithiasis causative gene SLC26A1 (Gee et al. 2016). In 348 individuals with nephrolithiasis or isolated nephrocalcinosis who are negative for the 30 genes mentioned above, recessive SLC26A1 causative variants were found in 2 patients (0.57%).

Large deletions and/or duplications appear to be relatively common in Human Gene Mutation Database (HGMD) for these genes: AGXT, OCRL, CLCN5, SLC3A1, SLC7A9 and HPRT1.

Large deletions and/or duplications have been documented in HGMD in these genes but are relatively uncommon: ATP6V0A4, CASR, KCNJ1, CLDN16, CLDN19, HNF4A, CYP24A1, FAM20A, SLC2A9, VDR, XDH and SLC26A1.

No large deletions or duplications have been reported in the other 10 genes of the current panel.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with nephrolithiasis or nephrocalcinosis. This test especially aids in a differential diagnosis of similar phenotypes by analyzing multiple genes simultaneously.

Diseases

Name Inheritance OMIM ID
Adenine Phosphoribosyltransferase Deficiency AR 614723
Amelogenesis Imperfecta, Type IG (Enamel-Renal Syndrome) AR 204690
Autosomal Recessive Hypophosphatemic Bone Disease AR 241530
Bartter Syndrome Antenatal Type 1 AR 601678
Bartter Syndrome Antenatal Type 2 AR 241200
Cystinuria AD 220100
Dent Disease 1 AR 300009
Dent Disease 2 AD,AR 300555
Familial Renal Hypouricemia AD 220150
Hypercalciuria, Absorptive, 2 AR 143870
Hypocalcemia, autosomal dominant AR 601198
Hypomagnesemia 5, Renal, With Ocular Involvement AD 248190
Idiopathic Hypercalcemia Of Infancy AR 143880
Lesch-Lyhan Syndrome XL 300322
Lowe Syndrome AR 309000
Maturity-Onset Diabetes Of The Young, Type 1 AR 125850
Nephrolithiasis, Calcium Oxalate AD 167030
Nephrolithiasis/Osteoporosis, Hypophosphatemic, 1 AD,AR 612286
Nephrolithiasis/Osteoporosis, Hypophosphatemic, 2 AD 612287
Osteopetrosis With Renal Tubular Acidosis AR 259730
Osteoporosis AR 166710
Primary Hyperoxaluria, Type I AD 259900
Primary Hyperoxaluria, Type II XL 260000
Primary Hyperoxaluria, Type III XL 613616
Primary Hypomagnesemia AR 248250
Renal Hypouricemia 2 AR 612076
Renal Tubular Acidosis With Progressive Nerve Deafness XL 267300
Renal Tubular Acidosis, Distal, Autosomal Dominant AD,AR 179800
Renal Tubular Acidosis, Distal, Autosomal Recessive XL 602722
Renal Tubular Acidosis, Distal, With Hemolytic Anemia AD 611590
Vitamin D-Dependent Rickets, Type 2 AR 277440
X-Linked Recessive Nephrolithiasis With Renal Failure AR 310468
Xanthinuria, Type I AR 278300

Related Test

Name
PGxome®

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
  • Hsi R.S., Stoller M.L. 2015. The Journal of Urology. 194: 1188-9. PubMed ID: 26279238
  • Human Gene Mutation Database (Bio-base).
  • Piccoli G.B. et al. 2016. Nephrology. 21: 97-107. PubMed ID: 26058976

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.

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

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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.

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