Nephronophthisis-Like Nephropathy-1 (NPHPL1) via the XPNPEP3 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
8365 XPNPEP3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8365XPNPEP381479 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

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-like nephropathy-1 (NPHPL1) patients develop a renal disease reminiscent of nephronophthisis within the first three decades of life (O’Toole et al. J Clin Invest 120:791-802, 2010). Renal biopsies from NPHPL1 patients showed characteristic features of nephronophthisis, such as thickening, splitting, and attenuation of the tubular basement membrane, atrophic tubules, and mild interstitial fibrosis, while renal ultrasound revealed increased echogenicity and cysts (O’Toole et al. 2010). Extrarenal features of NPHPL1 include hypertension, essential tremor, high frequency sensorineural hearing loss, and arachnoid cysts on brain imaging. In addition, severe cases of NPHPL1 might develop a mitochondrial disorder with isolated complex I deficiency activity in muscle, seizures, mental retardation, hypertrophic dilated cardiomyopathy, and chronic pancreatitis with pancreatic cysts or hepatic involvement (O’Toole et al. 2010).

Genetics

NPHPL1 is inherited in an autosomal recessive manner. Variants in the XPNPEP3 gene cause NPHPL1 (O’Toole et al. J Clin Invest 120:791-802, 2010). XPNPEP3 gene encodes a mitochondrial protein known as X-prolyl aminopeptidase 3 (XPNPEP3), which belongs to a family of X-prolyl aminopeptidases that utilize a metal cofactor and remove the N-terminal amino acid from peptides with a proline residue in the penultimate position (Ersahin et al. Arch Biochem Biophys 435:303-310, 2005). XPNPEP3 localizes to the mitochondria of the renal cells, yet it is predicted to have a cilia-related function. Biochemical studies demonstrated that several ciliary proteins are likely XPNPEP3 substrates (Ersahin et al. 2005; O’Toole et al. 2010). A frameshift variant and a splicing variant within the XPNPEP3 gene have been reported (O’Toole et al. 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity of this test is currently unknown.

Testing Strategy

This test provides full coverage of all coding exons of the XPNPEP3 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.

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 symptoms consistent with nephronophthisis-like nephropathy-1 and family members of patients who have known XPNPEP3 variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in XPNPEP3.

Gene

Official Gene Symbol OMIM ID
XPNPEP3 613553
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Nephronophthisis-Like Nephropathy 1 AR 613159

Citations

  • Ersahin, C., et.al. (2005). "Aminopeptidase P isozyme expression in human tissues and peripheral blood mononuclear cell fractions." Arch Biochem Biophys 435(2): 303-10. PubMed ID: 15708373
  • 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
  • O'Toole, J. F., et.al. (2010). "Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy." J Clin Invest 120(3): 791-802. PubMed ID: 20179356

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

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.

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