Nephronophthisis and Senior-Loken syndrome via the NPHP3 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
15263 NPHP3 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15263NPHP381479 81479 $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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

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Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Nephronophthisis (NPH) is the most common genetic cause of progressive renal failure in children and young adults. NPH is characterized by polyuria, growth retardation, and progressive deterioration of renal function with normal or slightly reduced kidney size (Hildebrandt et al. Nat Genet 17:149-153, 1997; Hildebrandt et al. J Am Soc Nephrol 20:23-35, 2009). Nephronophthisis type 3 (NPH3) (OMIM 604387) results in chronic renal failure in adolescents (Omran et al. Am J Hum Genet 66:118-127, 2000; Olbrich et al. Nat Genet 34:455-459, 2003). However, NPH3 has been also reported in five infants before five years of age (Tory et al. Kidney Int 75:839-847, 2009). Of note, a few cases of NPH3 have been associated with tapetoretinal degeneration known as Senior-Loken syndrome (OMIM# 606995) (Bergmann et al. Am J Hum Genet 82:959-970, 2008).

Genetics

NPH3 is inherited in an autosomal recessive manner. Variants in the NPHP3 gene cause NPH3 (Olbrich et al. Nat Genet 34:455-459, 2003). NPHP3 encodes a protein called nephrocystin-3. It has been indicated that nephrocystin-3 interacts with nephrocystin-1 and nephrocystin-4 (products of NPHP1 and NPHP4 genes respectively). Nephrocystin-3 may also have a role in microtubule regulation in monocilia (Olbrich et al. 2003). A mix of nonsense, frameshift, splicing and missense variants have been reported in NPHP3 (Tory et al. Kidney Int 75:839-847, 2009; Olbrich et al. 2003). Nephronophthisis exhibits locus heterogeneity. Nine NPH genes have been identified to date (NPHP1, INVS/NPHP2, NPHP3, NPHP4, IQCB1/NPHP5, CEP260/NPHP6, GLIS2/NPHP7, RPGRIP1L/NPHP8, and NEK8/NPHP9) (Hildebrandt et al. J Am Soc Nephrol 20:23-35, 2009).

Clinical Sensitivity - Sequencing with CNV PG-Select

Variants in NPHP3 gene are estimated to cause approximately ~1% of NPH cases (Hildebrandt et al. J Am Soc Nephrol 20:23-35, 2009).

Testing Strategy

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

This test provides full coverage of all coding exons of the NPHP3 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.

Indications for Test

Candidates for this test are patients with symptoms consistent with adolescent or juvenile NPH and the family members of patients who have known variants. Conclusive connections between clinical features and individual mutated genes have not yet been made. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NPHP3.

Gene

Official Gene Symbol OMIM ID
NPHP3 608002
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Adolescent Nephronophthisis AR 604387

Citations

  • Bergmann, C., et.al. (2008). "Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia." Am J Hum Genet 82(4): 959-70. PubMed ID: 18371931
  • Hildebrandt et al. 1997. PubMed ID: 9326933
  • Hildebrandt F. et al. 2009. Journal of the American Society of Nephrology : Jasn. 20: 23-35. PubMed ID: 19118152
  • Olbrich, H., et.al. (2003). "Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis." Nat Genet 34(4): 455-9. PubMed ID: 12872122
  • Omran, H., et.al. (2000). "Identification of a new gene locus for adolescent nephronophthisis, on chromosome 3q22 in a large Venezuelan pedigree." Am J Hum Genet 66(1): 118-27. PubMed ID: 10631142
  • Tory, K., et.al. (2009). "Mutations of NPHP2 and NPHP3 in infantile nephronophthisis." Kidney Int 75(8): 839-47. PubMed ID: 19177160

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

View Ordering Instructions

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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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