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Autosomal Dominant Polycystic Kidney Disease via MLPA of PKD1

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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TEST METHODS

MLPA

Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
2058 PKD1$540 81479 Add to Order

New York State Approved Test

Pricing Comments

Deletion and duplication analysis of PKD1 is performed using two commercial multiplex ligation-dependent amplification (MLPA) kits (MLPA P351-C1 and P352-D1 probemixes; MRC-Holland). The MLPA P351-C1 and P352-D1 probemixes used for this test do not contain probes for exons 1, 2, 4, 8, 17, 24, 28, 32, 34 and 45. Therefore, a deletion or duplication of a single exon in these regions cannot be detected.

Targeted Testing

For ordering sequencing of targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

Large deletions in PKD1 are relatively rare (Ariyurek et al. 2004; Rossetti et al. 2007; Audre'zet et al. 2012).

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Clinical Features

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited kidney disease with multisystem involvement. ADPKD is characterized by bilateral renal cysts accompanied by cysts in other organs including the liver, seminal vesicles, pancreas, and arachnoid membrane (Harris et al. 2011. PubMed ID: 20301424). Renal symptoms include hypertension, renal pain, and renal insufficiency. Nearly half of ADPKD patients have end-stage renal disease (ESRD) by age 60 years. The progressive growth of liver cysts is the most common extrarenal manifestation of ADPKD. The most important non-cystic manifestations of ADPKD are vascular and cardiac abnormalities including intracranial aneurysms, mitral valve prolapse, dilatation of the aortic root, dissection of the thoracic aorta, and abdominal wall hernias. The clinical spectrum of ADPKD is wide and substantial variability of disease severity can occur even within the same family.

Patients with ADPKD 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 autosomal recessive polycystic kidney disease (ARPKD) (caused by bi-allelic variants in the PKHD1 gene) (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.

Genetics

PKD1 and PKD2 are the two major causative genes for ADPKD (Rossetti et al. 2007. PubMed ID: 17582161; Audrézet et al. 2012. PubMed ID: 22508176). Accounting for a small fraction of ADPKD cases, GANAB and DNAJB11 are newly implicated in ADPKD (Porath et al. 2016. PubMed ID: 27259053; Cornec-Le Gall et al. 2018. PubMed ID: 29706351).

PKD1 (46 coding exons) encodes a member of the polycystin protein family, which plays an important role in renal tubular development. Genetic defects of PKD1 account for approximately 85% of genetically positive ADPKD cases and have been found across the whole coding region of the gene (Rossetti et al. 2007. PubMed ID: 17582161; Audrézet et al. 2012. PubMed ID: 22508176). In addition to missense substitutions and small in-frame changes, truncating changes (nonsense, canonical splice variants and frame-shifting small deletion/insertions) are the majority of PKD1 defects. Gross deletions have been also reported, but are relatively rare (<4% of pathogenic variants) (Ariyurek et al. 2004. PubMed ID: 14695542; Rossetti et al. 2007. PubMed ID: 17582161; Audrézet et al. 2012. PubMed ID: 22508176). The majority of PKD1 defects were found in single patients (Audrézet et al. 2012. PubMed ID: 22508176). De novo pathogenic variants account for about 10% of individuals with ADPKD in adulthood (Neumann et al. 2012. PubMed ID: 22367170).

Testing Strategy

As required, genomic DNA (gDNA) is extracted from the patient specimen. gDNA extracted from blood samples/submitted DNA from the patient is denatured and hybridized to MLPA probes specific to exonic or intronic regions of a particular gene(s). Each probe consists of two adjacent sequences that once hybridized to patient/reference DNA are ligated into a single probe. Fluorescently labeled PCR is then used to amplify each ligated probe using a common PCR primer set. The amplicon is then visualized during fragment separation using a capillary electrophoresis instrument. The relative peak height of each amplified probe from the patient’s sample is compared to four internal negative control results to determine relative copy number. For each patient sample the data for only the gene of interest is analyzed and reported.

Indications for Test

Candidates for this test are patients with ADPKD. Testing is also indicated for family members of patients who have known PKD1 pathogenic variants.

Gene

Official Gene Symbol OMIM ID
PKD1 601313
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Polycystic Kidney Disease 1 AD 173900

Related Test

Name
Autosomal Dominant Polycystic Kidney Disease via PKD1 Gene Sequencing with CNV Detection

CONTACTS

Genetic Counselors
Geneticist
Citations
  • Ariyurek et al. 2004. PubMed ID: 14695542
  • Audrézet et al. 2012. PubMed ID: 22508176
  • Audrézet et al. 2016. PubMed ID: 26139440
  • Bataille et al. 2011. PubMed ID: 22008521
  • Cornec-Le Gall et al. 2018. PubMed ID: 29706351
  • Harris et al. 2011. PubMed ID: 20301424
  • Neumann et al. 2012. PubMed ID: 22367170
  • Porath et al. 2016. PubMed ID: 27259053
  • Rossetti et al. 2007. PubMed ID: 17582161
  • Rossetti et al. 2009. PubMed ID: 19165178
  • Vujic et al. 2010. PubMed ID: 20558538
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TEST METHODS

Multiplex Ligation-Dependent Probe Amplification Assay

Test Procedure

As required, genomic DNA (gDNA) is extracted from the patient specimen. gDNA extracted from blood samples/submitted DNA from the patient is denatured and hybridized to MLPA probes specific to exonic or intronic regions of a particular gene(s). Each probe consists of two adjacent oligonucleotides that once hybridized to patient/reference DNA are ligated into a single DNA fragment.  Fluorescently labeled PCR is then used to amplify each ligated probe using a common PCR primer set. The amplicon is then sized using a capillary electrophoresis instrument. The relative peak height of each amplified probe from the patient’s sample is compared to four internal negative controls to determine relative copy number.  For each patient sample the data for only the gene(s) of interest is analyzed and reported.

Analytical Validity

MLPA enables the detection of relatively small deletion and insertion variants within a single exon of a given gene or within an entire gene.

Analytical Limitations

Interpretation of the test results is limited by the information that is currently available. Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.

Only the indicated gene or genes are analyzed. Test reports contain no information about other regions of the genome, including genes that are not requested, and genes that are not targeted. This test does not provide any information about deletions or duplications within repetitive elements.

Balanced translocations or inversions within a targeted gene, or large unbalanced translocations or inversions that extend beyond the genomic location of a targeted gene are not detected.

We cannot determine if the duplicated segment is inserted in tandem within the gene or inserted elsewhere in the genome. Similarly, we cannot determine the orientation of the duplicated segment (direct or inverted), and whether it will disrupt the open reading frame of the given gene.

For a single probe deletion or duplication we will compare MLPA results to sequencing results to ensure that no single nucleotide polymorphisms are underlying the specific probe, which may affect probe hybridization.

Any partial exonic deletions and duplications outside the probe binding sequence cannot be detected.

Impurities in the test and reference DNA samples can increase the chance of false positive or negative results. Where possible similar DNA extraction methods between test and reference samples are ideal for relative copy number analysis.

Our ability to detect minor copy number change, due for example to somatic mosaicism may be limited. 

Unless otherwise indicated, MLPA results are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about copy number changes in other tissues. 

We cannot be certain that the reference sequence(s) are correct. Exons, for example, may be misidentified.

We have confidence in our ability to track a specimen once it has been received by PreventionGenetics. However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics. 

Normal findings within a targeted gene do not rule out the clinical diagnosis of a genetic disease.

Genetic counseling to help explain test results to the patients and to discuss reproductive or medical options is recommended.

Order Kits

Ordering Options


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.

SPECIMEN TYPES
WHOLE BLOOD

(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.

DNA

(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.

CELL CULTURE

(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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