Autosomal Dominant Polycystic Kidney Disease via the PKD1 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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NGS Sequencing

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
3045 PKD1$1690.00 81407 Add to Order

New York State Approved Test

Pricing Comment

Our most cost-effective testing approach is NextGen sequencing with Sanger sequencing supplemented as needed to ensure sufficient coverage and to confirm NextGen calls that are pathogenic, likely pathogenic or of uncertain significance. If, however, full gene Sanger sequencing only is desired (for purposes of insurance billing or STAT turnaround time for example), please see link below for Test Code, pricing, and turnaround time information.

For Sanger Sequencing click here.
Targeted Testing

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

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Given that large deletions are relatively rare (Ariyurek et al. 2004; Rossetti et al. 2007; Audre'zet et al. 2012), the detection rate of PKD1 mutations through our sequencing method is expected to be nearly equal to the reported overall detection rate of PKD1 mutations in ADPKD, which is approximately 75% (Rossetti et al. 2007; Audre'zet et al. 2012).

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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
2058 PKD1$540.00 81479 Add to Order
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; OMIM# 173900) 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. 2002). Renal symptoms include hypertension, renal pain, and renal insufficiency. Nearly half of all 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. Compared with PKD1-related ADPKD, patients with PKD2 defects have approximately 20 years longer renal survival (median age at onset of ESRD: 58 years vs 79 years) (Cornec-Le Gall et al. 2013). Sporadic cases account for about 10% of individuals with ADPKD in adulthood (Neumann et al. 2012).

Patients with ADPKD typically have onset of symptoms in adulthood.  In some rare cases, however, patients with two causative PKD1 mutations in trans may have clinical features similar to those of patients with autosomal recessive polycystic kidney disease (caused by mutations in the PKHD1 gene) (Rossetti et al. 2009; Vujic et al. 2010). In these rare cases, symptoms may appear in early childhood or even in utero.


Mutations in either the PKD1 or PKD2 gene cause ADPKD (Rossetti et al. 2007; Audrézet et al. 2012). PKD1 has 46 exons that encode 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 mutation-positive ADPKD and have been found across the whole coding region of the gene (Rossetti et al. 2007; Audrézet et al. 2012). In addition to missense mutations and small in-frame changes, truncated mutations (nonsense, typical splicing mutations and frame-shifting small deletion/insertions) are the majority of PKD1 defects (Rossetti et al. 2007; Audrézet et al. 2012). Gross deletions have been also reported, but are relatively rare (probably 1-4% of definite pathogenic mutations) (Ariyurek et al. 2004; Rossetti et al. 2007; Audrézet et al. 2012). The majority of PKD1 defects were found in single patients (Audrézet et al. 2012).

Testing Strategy

For this Next Generation (NextGen) test, the full coding regions plus ~20 bp of non-coding DNA flanking each exon are sequenced for the gene listed below. Sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization kit, followed by massively parallel sequencing of the captured DNA fragments. Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads. All pathogenic, likely pathogenic, or variants of uncertain significance are confirmed by Sanger sequencing.

Indications for Test

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


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


Name Inheritance OMIM ID
Polycystic Kidney Disease 1 173900


Genetic Counselors
  • Ariyurek Y, Leeuwen IL, Spruit L, Ravine D, Breuning MH, Peters DJM. 2004. Large deletions in the polycystic kidney disease 1 (PKD1) gene. Human Mutation 23: 99–99. PubMed ID: 14695542
  • Audrézet M-P, Cornec-Le Gall E, Chen J-M, Redon S, Quéré I, Creff J, Bénech C, Maestri S, Meur Y Le, Férec C. 2012. Autosomal dominant polycystic kidney disease: Comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Human Mutation 33: 1239–1250. PubMed ID: 22508176
  • Cornec-Le Gall E, Audrezet M-P, Chen J-M, Hourmant M, Morin M-P, Perrichot R, Charasse C, Whebe B, Renaudineau E, Jousset P, Guillodo M-P, Grall-Jezequel A, et al. 2013. Type of PKD1 Mutation Influences Renal Outcome in ADPKD. Journal of the American Society of Nephrology 24: 1006–1013. PubMed ID: 23431072
  • Harris PC, Torres VE. 2011. Polycystic Kidney Disease, Autosomal Dominant. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301424
  • Neumann HPH, Bacher J, Nabulsi Z, Ortiz Brüchle N, Hoffmann MM, Schaeffner E, Nürnberger J, Cybulla M, Wilpert J, Riegler P, Corradini R, Kraemer-Guth A, et al. 2012. Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes. International Urology and Nephrology 44: 1753–1762. PubMed ID: 22367170
  • Rossetti S, Consugar MB, Chapman AB, Torres VE, Guay-Woodford LM, Grantham JJ, Bennett WM, Meyers CM, Walker DL, Bae K, Zhang Q, Thompson PA, et al. 2007. Comprehensive Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease. Journal of the American Society of Nephrology 18: 2143–2160. PubMed ID: 17582161
  • Rossetti S, Kubly VJ, Consugar MB, Hopp K, Roy S, Horsley SW, Chauveau D, Rees L, Barratt TM, Hoff WG van’t, Niaudet WP, Torres VE, et al. 2009. Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease. Kidney International 75: 848–855. PubMed ID: 19165178
  • Vujic M, Heyer CM, Ars E, Hopp K, Markoff A, Orndal C, Rudenhed B, Nasr SH, Torres VE, Torra R, Bogdanova N, Harris PC. 2010. Incompletely Penetrant PKD1 Alleles Mimic the Renal Manifestations of ARPKD. J Am Soc Nephrol 21: 1097–1102. PubMed ID: 20558538
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NextGen Sequencing using PG-Select Capture Probes

Test Procedure

We use a combination of Next Generation Sequencing (NGS) and Sanger sequencing technologies to cover the full coding regions of the listed genes plus ~20 bases of non-coding DNA flanking each exon.  As required, genomic DNA is extracted from the patient specimen.  For NGS, patient DNA corresponding to these regions is captured using an optimized set of DNA hybridization probes.  Captured DNA is sequenced using Illumina’s Reversible Dye Terminator (RDT) platform (Illumina, San Diego, CA, USA).  Regions with insufficient coverage by NGS are covered by Sanger sequencing.  All pathogenic, likely pathogenic, or variants of uncertain significance are confirmed by Sanger sequencing.

For Sanger sequencing, Polymerase Chain Reaction (PCR) is used to amplify targeted regions.  After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Patient DNA sequence is aligned to the genomic reference sequence for the indicated gene region(s). All differences from the reference sequences (sequence variants) are assigned to one of five interpretation categories, listed below, per ACMG Guidelines (Richards et al. 2015).

(1) Pathogenic Variants
(2) Likely Pathogenic Variants
(3) Variants of Uncertain Significance
(4) Likely Benign Variants
(5) Benign, Common Variants

Human Genome Variation Society (HGVS) recommendations are used to describe sequence variants (  Rare variants and undocumented variants are nearly always classified as likely benign if there is no indication that they alter protein sequence or disrupt splicing.

Analytical Validity

As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides.

In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable.   

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.

When Sanger sequencing does not reveal any difference from the reference sequence, or when a sequence variant is homozygous, we cannot be certain that we were able to detect both patient alleles.  Occasionally, a patient may carry an allele which does not amplify, due to a large deletion or insertion.   In these cases, the report will contain no information about the second allele.  Our Sanger and NGS Sequencing tests are generally not capable of detecting Copy Number Variants (CNVs).

We sequence all coding exons for each given transcript, plus ~20 bp of flanking non-coding DNA for each exon.  Test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions or any currently uncharacterized alternative exons.

In most cases, we are unable to determine the phase of sequence variants.  In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants due to somatic mosaicism is limited.  Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR.

Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes from whole blood).   Test reports contain no information about the DNA sequence in other cell-types.

We cannot be certain that the reference sequences are correct.

Rare, low probability interpretations of sequencing results, such as for example the occurrence of de novo mutations in recessive disorders, are generally not included in the reports.

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.

Methylation-specific Multiplex Ligation-dependent Probe Amplification

Test Procedure

Multiplex Ligation-dependent Probe Amplification (MLPA) is a semi-quantitative technique that is used to determine the relative copy number of up to 60 DNA sequences in a single multiplex PCR-based reaction. It is based on amplification of up to 60 probes, each of which detects a specific complementary DNA sequence of approximately 60 bp in length (often exons in genes of interest). Briefly, each MLPA probe is made up of two half-probes that hybridize immediately adjacent to each other at the target DNA. These adjacent probes are then ligated into one single probe before being amplified in a PCR reaction. Multiplexing is achieved by different probes varying in sizes ranging from 150-500 bp, that are all amplified using a common PCR primer pair. One of the PCR primers is fluorescently labelled enabling separation and detection of the amplification products in a capillary electrophoresis instrument. The peaks heights of the amplification products of the target DNA sequence is then compared to the peak heights in various reference DNA samples. A deletion or a duplication is inferred from the relative decrease or increase in peak height respectively.

A modified MLPA technique termed Methylation-specific MLPA (MS-MLPA) is used to detect both the copy number and methylation status of up to 50 DNA sequences in a single multiplex PCR-based reaction. The basic principle of MS-MLPA is very similar to MLPA except that the target DNA sequences recognized by the MS-MLPA probes contain restriction sites for enzymes such a HhaI or HpaII that are sensitive to cytosine methylation of one CpG site in their recognition sequence. When target DNA is digested with these enzymes a probe amplification product will only be obtained if the CpG site is methylated. The level of methylation is determined by the ratio of the relative peak area for each target probe from digested vs undigested DNA sample.

Analytical Validity

MS-MLPA is a robust method that is widely used for the clinical diagnosis of several genetic imprinting disorders like Prader-Willi syndrome /Angelman syndrome, Beckwith-Widemann syndrome, Russell-Silver syndrome, Lynch syndrome and Albright hereditary osteodystrophy. MS-MLPA has several advantages over other assays such as MS-PCR based on bisulphite sequencing, southern blotting, and methylation analysis including PCR following restriction digestion with methylation sensitive enzyme. MS-MLPA investigates methylation status at multiple loci, thereby reducing the risk for false positive or false negative results due single nucleotide polymorphisms (SNPs) at the probe binding sequence.

Analytical Limitations

Both MLPA and MS-MLPA will not detect point mutations in sequences recognized by the probes. In addition it will not detect inversions, balanced translocations or copy number changes that lie outside the sequence detected by the MLPA probes.

MLPA probes are sensitive to changes within the sequence detected by the probe. A single nucleotide change (such as SNPs or pathogenic mutations) very close to the probe ligation site can prevent ligation of the two oligonucleotide probes. In addition, sequence changes further from the ligation site can affect probe binding and hence decrease probe signal mimicking a deletion.

MLPA is sensitive to DNA characteristics such as impurities, method used for DNA isolation, salt concentrations in solution, and degree of DNA degradation.  The effect of these characteristics can be minimized by using the same DNA extraction methods for all samples analyzed by this method and by matching the test and control DNA from the same source.

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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.
  • 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.


(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.


(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.


(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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