Invitae Nephrolithiasis Panel
Test description
The Invitae Nephrolithiasis Panel analyzes genes that are associated with nephrolithiasis/kidney stone disease.
Genes tested
ADCY10 AGXT ALPL APRT ATP6V0A4 ATP6V1B1 CA2 CASR CLCN5 CLDN16 CLDN19 CYP24A1 FAM20A GPHN GRHPR HOGA1 HPRT1 KCNJ1 MOCOS MOCS1 OCRL PREPL SLC12A1 SLC22A12 SLC26A1 SLC2A9 SLC34A1 SLC34A3 SLC3A1 SLC4A1 SLC7A9 SLC9A3R1 UMOD VDR XDH
Order test
Primary panel (35 genes)
Customized gene selection (0 included, 0 excluded)
ADCY10 AGXT ALPL APRT ATP6V0A4 ATP6V1B1 CA2 CASR CLCN5 CLDN16 CLDN19 CYP24A1 FAM20A GPHN GRHPR HOGA1 HPRT1 KCNJ1 MOCOS MOCS1 OCRL PREPL SLC12A1 SLC22A12 SLC26A1 SLC2A9 SLC34A1 SLC34A3 SLC3A1 SLC4A1 SLC7A9 SLC9A3R1 UMOD VDR XDH
Clinical information
Disorders tested
- Familial idiopathic hypercalciuria
- Primary hyperoxaluria, type 1 (PH1)
- Hypophosphatasia
- Adenine phosphoribosyltransferase (APRT)
- Distal renal tubular acidosis (dRTA)
- Distal renal tubular acidosis (dRTA) with progressive nerve deafness
- Carbonic anhydrase 2 (CA2) deficiency
- Familial hypocalciuric hypercalcemia (FHH), autosomal dominant hypocalcemia (ADH), ADH with Bartter syndrome, neonatal severe hyperparathyroidism (NSHPT)
- Dent disease complex
- Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC)
- Infantile hypercalcemia
- Enamel-renal syndrome
- Molybdenum cofactor deficiency
- Primary hyperoxaluria, type 2 (PH2)
- Primary hyperoxaluria type 3 (PH3)
- HPRT1 deficiency which includes a spectrum of Lesch Nyhan syndrome to isolated hyperuricemia with gout
- Bartter syndrome type 2 (BSII)
- Xanthinuria type II
- Lowe syndrome
- Congenital myasthenic syndrome 22 (CMS22), hypotonia-cystinuria syndrome
- Bartter syndrome type 1
- Renal hypouricemia
- Calcium oxalate urolithiasis, nephrolithiasis
- Familial hypouricemia
- Infantile hypercalcemia, hypophosphatemic nephrolithiasis/osteoporosis
- Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)
- Cystinuria, hypotonia-cystinuria deletion syndrome
- Distal renal tubular acidosis (dRTA), dRTA with haemolytic anemia
- Cystinuria type B
- Hypophosphatemic nephrolithiasis and osteoporosis
- Tubulointerstitial kidney disease (ADTKD), medullary cystic kidney disease type 2 (MCKD2)
- Vitamin D-dependent rickets type 2A (VDDR2A)
- Xanthinuria type I
Clinical description
To view the complete clinical description of this panel, click here.
Inheritance
Genes on the Nephrolithiasis panel can be inherited in an autosomal dominant, autosomal recessive or X-linked pattern. Several genes on the Nephrolithiasis panel can be inherited in either autosomal dominant or autosomal recessive pattern. Recessive genes are more likely to be the cause for affected infants and children and autosomal dominant inheritance for adult onset forms (PMID: 25296721, 26787776).
References
- Braun, DA, et al. Prevalence of Monogenic Causes in Pediatric Patients with Nephrolithiasis or Nephrocalcinosis. Clin J Am Soc Nephrol. 2016; 11(4):664-72. PMID: 26787776
- Moayyeri, A, et al. Metabolomic Pathways to Osteoporosis in Middle-Aged Women: A Genome-Metabolome-Wide Mendelian Randomization Study. J. Bone Miner. Res. 2018; 33(4):643-650. PMID: 29232479
- Gambaro, G, et al. Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement. J. Nephrol. 2016; 29(6):715-734. PMID: 27456839
- Worcester, EM, Coe, FL. Nephrolithiasis. Prim. Care. 2008; 35(2):369-91, vii. PMID: 18486720
- Halbritter, J, et al. Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J. Am. Soc. Nephrol. 2015; 26(3):543-51. PMID: 25296721
- Sorokin, I, et al. Epidemiology of stone disease across the world. World J Urol. 2017; 35(9):1301-1320. PMID: 28213860
- Eggermann, T, et al. Cystinuria: an inborn cause of urolithiasis. Orphanet J Rare Dis. 2012; 7:19. PMID: 22480232
- Bökenkamp, A, Ludwig, M. The oculocerebrorenal syndrome of Lowe: an update. Pediatr. Nephrol. 2016; 31(12):2201-2212. PMID: 27011217
- Jinnah, HA, et al. The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases. Mutat. Res. 2000; 463(3):309-26. PMID: 11018746
- Edvardsson, VO, et al. Hereditary causes of kidney stones and chronic kidney disease. Pediatr. Nephrol. 2013; 28(10):1923-42. PMID: 23334384
- Policastro, LJ, et al. Personalized Intervention in Monogenic Stone Formers. J. Urol. 2018; 199(3):623-632. PMID: 29061541
Assay
Assay and technical information
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
| Gene | Transcript reference | Sequencing analysis | Deletion/Duplication analysis |
|---|---|---|---|
| ADCY10 | NM_018417.5 | ||
| AGXT | NM_000030.2 | ||
| ALPL | NM_000478.5 | ||
| APRT | NM_000485.2 | ||
| ATP6V0A4 | NM_020632.2 | ||
| ATP6V1B1 | NM_001692.3 | ||
| CA2 | NM_000067.2 | ||
| CASR | NM_000388.3 | ||
| CLCN5 | NM_000084.4 | ||
| CLDN16 | NM_006580.3 | ||
| CLDN19 | NM_148960.2 | ||
| CYP24A1 | NM_000782.4 | ||
| FAM20A | NM_017565.3 | ||
| GPHN | NM_020806.4 | ||
| GRHPR | NM_012203.1 | ||
| HOGA1 | NM_138413.3 | ||
| HPRT1 | NM_000194.2 | ||
| KCNJ1 | NM_000220.4 | ||
| MOCOS | NM_017947.2 | ||
| MOCS1 | NM_001075098.3 | ||
| OCRL | NM_000276.3 | ||
| PREPL | NM_006036.4 | ||
| SLC12A1 | NM_000338.2 | ||
| SLC22A12 | NM_144585.3 | ||
| SLC26A1 | NM_213613.3 | ||
| SLC2A9 | NM_020041.2 | ||
| SLC34A1 | NM_003052.4 | ||
| SLC34A3 | NM_080877.2 | ||
| SLC3A1 | NM_000341.3 | ||
| SLC4A1 | NM_000342.3 | ||
| SLC7A9 | NM_014270.4 | ||
| SLC9A3R1 | NM_004252.4 | ||
| UMOD | NM_003361.3 | ||
| VDR | NM_001017535.1 | ||
| XDH | NM_000379.3 |
References
- Braun, DA, et al. Prevalence of Monogenic Causes in Pediatric Patients with Nephrolithiasis or Nephrocalcinosis. Clin J Am Soc Nephrol. 2016; 11(4):664-72. PMID: 26787776
- Bökenkamp, A, Ludwig, M. The oculocerebrorenal syndrome of Lowe: an update. Pediatr. Nephrol. 2016; 31(12):2201-2212. PMID: 27011217
- Edvardsson, VO, et al. Hereditary causes of kidney stones and chronic kidney disease. Pediatr. Nephrol. 2013; 28(10):1923-42. PMID: 23334384
- Eggermann, T, et al. Cystinuria: an inborn cause of urolithiasis. Orphanet J Rare Dis. 2012; 7:19. PMID: 22480232
- Gambaro, G, et al. Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement. J. Nephrol. 2016; 29(6):715-734. PMID: 27456839
- Halbritter, J, et al. Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J. Am. Soc. Nephrol. 2015; 26(3):543-51. PMID: 25296721
- Jinnah, HA, et al. The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases. Mutat. Res. 2000; 463(3):309-26. PMID: 11018746
- Moayyeri, A, et al. Metabolomic Pathways to Osteoporosis in Middle-Aged Women: A Genome-Metabolome-Wide Mendelian Randomization Study. J. Bone Miner. Res. 2018; 33(4):643-650. PMID: 29232479
- Policastro, LJ, et al. Personalized Intervention in Monogenic Stone Formers. J. Urol. 2018; 199(3):623-632. PMID: 29061541
- Sorokin, I, et al. Epidemiology of stone disease across the world. World J Urol. 2017; 35(9):1301-1320. PMID: 28213860
- Worcester, EM, Coe, FL. Nephrolithiasis. Prim. Care. 2008; 35(2):369-91, vii. PMID: 18486720
