Autosomal Recessive Polycystic Kidney Disease (ARPKD) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10463 DZIP1L 81479,81479 Order Options and Pricing
PKHD1 81408,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10463Genes x (2)81479 81408, 81479 $890 Order Options and Pricing

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

Autosomal recessive polycystic kidney disease (ARPKD) is a hepatorenal fibrocystic disorder characterized by enlarged kidneys with collecting duct cysts and congenital hepatic fibrosis due to ductal plate malformation (DPM) during development (Bergmann. 2017. PubMed ID: 29479522; Sweeney et al. 1993. PubMed ID: 20301501). Arterial hypertension often develops during the first months of life and affects up to 80% of children with ARPKD. Severity varies widely; and the most severe cases are often neonatal lethal, accounting for approximately 30% of ARPKD patients with pathogenic variants in PKHD1. Diagnosis is often made pre- or neonatally although some cases are diagnosed in childhood or adult life. Many who survive the newborn period progress to end stage renal disease (ESRD).

Genetics

PKHD1 is the primary causative gene for ARPKD (Bergmann. 2017. PubMed ID: 29479522; Ward et al. 2002. PubMed ID: 11919560). Accounting for a small fraction of genetically positive cases, DZIP1L was newly identified as the second causative gene for ARPKD (Lu et al. 2017. PubMed ID: 28530676; Hartung and Guay-Woodford. 2017. PubMed ID: 28736432).

The PKHD1 gene encodes fibrocystin, a ciliary-localized membrane protein involved in a wide range of cellular functions including cell-to-cell adhesion and proliferation, acting as a membrane-bound receptor, and microtubule organization and/or in mechano- or chemosensation (Bergmann. 2017. PubMed ID: 29479522). Documented pathogenic variants in PKHD1 include truncating changes (nonsense, typical splicing variants and frame-shifting small deletion/insertions) and missense substitutions throughout the length of the gene (Human Gene Mutation Database). Multi-exon deletions and duplications occur, but are relatively rare (probably <5% of all pathogenic variants) (Bergmann et al. 2005. PubMed ID: 16199545). No obvious genotype-phenotype correlations have been established to date, but patients with two protein-truncating variants usually have the most severe disease with perinatal or neonatal mortality.

The DZIP1L gene encodes DAZ interacting protein 1‑like protein, the impairment of which is associated with ciliary trafficking defects and renal cystogenesis. Documented pathogenic variants in DZIP1L include truncating changes (nonsense variants and frame-shifting small deletions/insertions) and missense substitutions (Lu et al. 2017. PubMed ID: 28530676). No large deletions or duplications have been reported yet.

Patients with a heterozygous pathogenic variant in autosomal dominant polycystic kidney disease (ADPKD) genes such as PKD1 and PKD2 typically have onset of symptoms in adulthood. In some rare cases, however, patients with bi-allelic PKD1 variants may have clinical features similar to those of patients with ARPKD (Rossetti et al. 2009. PubMed ID: 19165178; Vujic et al. 2010. PubMed ID: 20558538; Audrézet et al. 2016. PubMed ID: 26139440). In these rare cases, symptoms may appear in early childhood or even in utero. Therefore, testing for ADPKD genes have been recommended for early onset PKD patients, especially when testing of PKHD1 or DZIP1L returns negative.

Clinical Sensitivity - Sequencing with CNV PGxome

Homozygous or compound heterozygous pathogenic variants in PKHD1 can be found in ~80% of autosomal recessive polycystic kidney disease (ARPKD) patients regardless of disease severity. Approximately 95% of affected individuals were found to have at least one pathogenic variant in PKHD1 (Bergmann. 2017. PubMed ID: 29479522). Multi-exon deletions and duplications occur, but are relatively rare (probably <5% of all pathogenic variants) (Bergmann et al. 2005. PubMed ID: 16199545).

Defects in the DZIP1L gene were found in only two of 743 (~0.3%) unrelated individuals with suspected ARPKD or sporadic PKD (Lu et al. 2017. PubMed ID: 28530676). No large deletions or duplications have been reported yet.

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 ARPKD.

Genes

Official Gene Symbol OMIM ID
DZIP1L 617570
PKHD1 606702
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Audrézet et al. 2016. PubMed ID: 26139440
  • Bergmann et al. 2005. PubMed ID: 16199545
  • Bergmann. 2017. PubMed ID: 29479522
  • Hartung and Guay-Woodford. 2017. PubMed ID: 28736432
  • Human Gene Mutation Database (Bio-base).
  • Lu et al. 2017. PubMed ID: 28530676
  • Rossetti et al. 2009. PubMed ID: 19165178
  • Sweeney et al. 1993. PubMed ID: 20301501
  • Vujic et al. 2010. PubMed ID: 20558538
  • Ward et al. 2002. PubMed ID: 11919560

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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