Test Id : CKDGP

For prenatal specimens only:

If an amniotic fluid specimen or nonconfluent cultures are received, amniotic fluid culture for a genetic test will be performed at an additional charge.

If a chorionic villi specimen is received, fibroblast culture for a genetic test will be performed at an additional charge.

For any prenatal specimen received, maternal cell contamination testing will be performed at an additional charge.

Targeted testing for familial variants (also called site-specific or known mutations/variants testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen as this must be a different order number than the prenatal specimen.

Specimen preferred to arrive within 96 hours of collection.

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.

Submit only 1 of the following specimens:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Prenatal Specimens:

Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional information:

1. If amniotic fluid or nonconfluent cultures are received, CULAF / Culture for Genetic Testing, Amniotic Fluid will be added at an additional charge.

2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

Additional Information:

1. If nonconfluent cultures are received, CULFB / Fibroblast Culture for Biochemical or Molecular Testing will be added at an additional charge.

2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

Acceptable:

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information: All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

• Informed Consent for Genetic Testing
• Informed Consent for Genetic Testing (Spanish)
• Hereditary Renal Genetic Testing Patient Information
• Targeted Genes and Methodology Details for Cystic Kidney Disease Gene Panel

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Hereditary Renal Genetic Testing Patient Information (T918)

3. If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.

Blood: 1 mL; Amniotic fluid/CVS: See Specimen Required

Providing a genetic evaluation for patients with a personal or family history of cystic kidney disease

Establishing a diagnosis of hereditary cystic kidney disease

This test utilizes next-generation sequencing to detect single nucleotide, deletion-insertion, and copy number variants in 45 genes associated with cystic kidney disease: ALG8, ALG9, ANKS6, BICC1, CEP164, CEP290, CEP83, COL4A1, CRB2, DCDC2, DNAJB11, DZIP1L, GANAB, GLIS2, HNF1B, INVS, IQCB1, JAG1, LRP5, MAPKBP1, NEK8, NOTCH2, NPHP1, NPHP3, NPHP4, OFD1, PAX2, PKD1, PKD2, PKHD1, PRKCSH, RPGRIP1L, SDCCAG8, SEC61A1, SEC63, TMEM67, TRAF3IP1, TSC1, TSC2, TTC21B, UMOD, VHL, WDR19, WDR35, XPNPEP3. See Targeted Genes and Methodology Details for Cystic Kidney Disease Gene Panel in Method Description for additional details.

For prenatal specimens only:

If an amniotic fluid specimen or nonconfluent cultures are received, amniotic fluid culture for a genetic test will be performed at an additional charge.

If a chorionic villi specimen is received, fibroblast culture for a genetic test will be performed at an additional charge.

For any prenatal specimen received, maternal cell contamination testing will be performed at an additional charge.

Hereditary forms of cystic kidney disease have several underlying genetic etiologies and may present in childhood or adulthood, with or without extrarenal features. The two most common categories of hereditary cystic kidney disease are the ciliopathic disorders and the phakomatoses.(1)

Ciliopathic disorders causing cystic kidney disease include polycystic kidney disease (PKD), nephronophthisis (NPHP), and medullary cystic kidney disease (MCKD). The PKD1 and PKD2 genes cause the majority of autosomal dominant PKD (ADPKD), while the GANAB and DNAJB11 genes are implicated in a minority of cases.(2,3) The PKHD1 gene is the major gene associated with autosomal recessive PKD (ARPKD), while DZIP1L has been more recently identified as a secondary cause.(4) ARPKD is often diagnosed in utero due to oligohydramnios. NPHP is an autosomal recessive condition characterized by cystic kidney disease, inflammation, fibrosis, and progression to kidney failure. MCKD is an autosomal dominant condition characterized by cysts in the medullary region of the kidney, kidney tubule fibrosis, hyperuricemia, and slowly worsening kidney function. Genes included on this panel for MCKD include HNF1B, UMOD, and SEC61A1 (note the MUC1 gene is not included on this panel).

Phakomatoses, also known as neurocutaneous syndromes, are a broad group of hereditary disorders characterized by involvement of structures that arise from the embryonic ectoderm (central nervous system, skin, and eyes). Cystic renal lesions are common in these disorders. Phakomatoses genes included on this panel are the TSC1 and TSC2 tumor suppressor genes associated with tuberous sclerosis complex (TSC) and the VHL gene associated with von Hippel-Lindau syndrome.

An interpretive report will be provided.

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(5) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Correlations:
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact Mayo Clinic Laboratories genetic counselors at 800-533-1710.

Technical Limitations:
Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

Deletion/Duplication Analysis:

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

Genes may be added or removed based on updated clinical relevance. Refer to the Targeted Genes and Methodology Details for Cystic Kidney Disease Gene Panel for the most up to date list of genes included in this test. r detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

Reclassification of Variants:
At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time.

Variant Evaluation:
Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(5) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgement.

Rarely, incidental findings or secondary findings may implicate another predisposition or presence of active disease. Incidental findings may include but are not limited to, results related to the sex chromosomes. These findings will be carefully reviewed to determine whether they will be reported.

1. Dillman JR, Trout AT, Smith EA, Towbin AJ: Hereditary renal cystic disorders: Imaging of the kidneys and beyond. Radiographics. May-Jun 2017;37(3):924-946. doi: 10.1148/rg.2017160148

2. Porath B, Gainullin VG, Cornec-Le Gall E, et al: Mutations in GANAB, encoding the glucosidase IIa subunit, cause autosomal-dominant polycystic kidney and liver disease. Am J Hum Genet. 2016 Jun 2;98(6):1193-1207. doi: 10.1016/j.ajhg.2016.05.004

3. Cornec-Le Gall E, Olson RJ, Besse W, et al: Monoallelic mutations to DNAJB11 cause atypical autosomal-dominant polycystic kidney disease. Am J Hum Genet. 2018 May 3;102(5):832-844. doi: 10.1016/j.ajhg.2018.03.013

4. Lu H, Rondon Galeano M, Ott E, et al: Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease. Nat Genet. 2017 Jul;49(7):1025-1034. doi: 10.1038/ng.3871

5. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424. doi: 10.1038/gim.2015.30

Capture-based and amplicon-based next-generation sequencing (NGS is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Cystic Kidney Disease Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

Genes analyzed: ALG8, ALG9, ANKS6, BICC1, CEP164, CEP290, CEP83, COL4A1, CRB2, DCDC2, DNAJB11, DZIP1L, GANAB, GLIS2, HNF1B, INVS, IQCB1, JAG1, LRP5, MAPKBP1, NEK8, NOTCH2, NPHP1, NPHP3, NPHP4, OFD1, PAX2, PKD1, PKD2, PKHD1, PRKCSH, RPGRIP1L, SDCCAG8, SEC61A1, SEC63, TMEM67, TRAF3IP1, TSC1, TSC2, TTC21B, UMOD, VHL, WDR19, WDR35, XPNPEP3

Varies

• Authorized users can sign in to Test Prices for detailed fee information.
• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their account representative. For assistance, contact Customer Service.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

81404

81405

81406 x 6

81407 x 4

81408 x 3

81479

81265-Maternal cell contamination (if appropriate)

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88235-Amniotic Fluid culture (if appropriate)

81479 (if appropriate for government payers)