Test Catalog

Test Id : CDKZ

CDKN1C Gene, Full Gene Analysis, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirming a clinical diagnosis of Beckwith-Wiedemann syndrome following a normal result on methylation analysis

 

Confirming a clinical diagnosis of IMAGe (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies) syndrome

 

Confirming a clinical diagnosis of Russell-Silver syndrome following a normal result on methylation analysis and uniparental disomy (UPD) 7 studies

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For prenatal specimens only:

-If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added at an additional charge.

-If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added at an additional charge.

 

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

 

If a skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR) followed by DNA Sequencing

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

CDKN1C Gene, Full Gene Analysis

Aliases
Lists additional common names for a test, as an aid in searching

Beckwith-Wiedemann syndrome (BWS).

BWS (Beckwith-Wiedemann syndrome)

IMAGe syndrome

KIP2

P57

CDKMS

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For prenatal specimens only:

-If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added at an additional charge.

-If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added at an additional charge.

 

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

 

If a skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

This test is for CDKN1C gene sequencing. For a full evaluation of a possible diagnosis of Beckwith-Wiedemann Syndrome, the recommended first-tier test is BWRS / Beckwith-Wiedemann Syndrome/Russell-Silver Syndrome, Molecular Analysis, Varies.

Additional Testing Requirements

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.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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

 

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

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 flask or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Prenatal Specimens

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing. Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. Central time on Friday in order to be processed appropriately.

 

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional information:

1. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid. An additional 2 to 3 weeks is required to culture amniotic fluid before genetic testing can occur.

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. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Genetic Test. An additional 2 to 3 weeks is required to culture chorionic villi before genetic testing can occur.

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: 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.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

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. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL; Other specimen types: See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirming a clinical diagnosis of Beckwith-Wiedemann syndrome following a normal result on methylation analysis

 

Confirming a clinical diagnosis of IMAGe (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies) syndrome

 

Confirming a clinical diagnosis of Russell-Silver syndrome following a normal result on methylation analysis and uniparental disomy (UPD) 7 studies

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For prenatal specimens only:

-If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added at an additional charge.

-If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added at an additional charge.

 

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

 

If a skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The CDKN1C gene is an imprinted gene that has been associated with Beckwith-Wiedemann syndrome (BWS), IMAGe (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies) syndrome, and Russell-Silver syndrome (RSS). Imprinting describes a difference in gene expression based on parent of origin. The majority of autosomal genes exhibit biallelic (maternal and paternal) expression, whereas imprinted genes are normally expressed from only one parent. CDKN1C is typically expressed on the maternally inherited allele.

 

Beckwith-Wiedemann Syndrome:

Beckwith-Wiedemann syndrome is a disorder characterized by prenatal and/or postnatal overgrowth, neonatal hypoglycemia, congenital malformations, and an increased risk for embryonal tumors. Physical findings are variable and can include abdominal wall defects, macroglossia, and hemihyperplasia. The predisposition for tumor development is associated with specific tumor types such as adrenal carcinoma, nephroblastoma (Wilms tumor), hepatoblastoma, and rhabdomyosarcoma. In infancy, BWS has a mortality rate of approximately 20%.

 

Most cases of BWS are caused by hypomethylation of LIT1, paternal uniparental disomy of chromosome 11, or hypermethylation of H19. Approximately 5% to 10% of sporadic BWS cases and approximately 40% of BWS cases with a positive family history are caused by CDKN1C variants. The appropriate first-tier test in the evaluation of a possible diagnosis of BWS is BWRS / Beckwith-Wiedemann Syndrome/Russell-Silver Syndrome, Molecular Analysis, Varies. This test may be considered when the results of BWS methylation analysis are negative, and there is still a strong clinical suspicion of BWS.

 

IMAGe Syndrome:

Variants in the CDKN1C gene have also been associated with IMAGe syndrome. The CDKN1C variants associated with IMAGe syndrome tend to be missense variants occurring in the PCNA-binding domain of the gene. Not every individual with a clinical diagnosis of IMAGe syndrome will have an identifiable CDKN1C variant.

 

Russell-Silver Syndrome:

Russell-Silver syndrome is a rare genetic condition with an incidence of approximately 1 in 100,000. RSS is characterized by pre- and postnatal growth delay with normal head circumference, characteristic facies, fifth finger clinodactyly, and asymmetry of the face, body, and/or limbs. Less commonly observed clinical features include cafe au lait spots, genitourinary anomalies, motor, speech, cognitive delays, and hypoglycemia.

 

RSS is a genetically heterogeneous condition that is associated with genetic and epigenetic alterations at chromosome 7 and the chromosome 11p15.5 region. The majority of cases of RSS are sporadic, although familial cases have been reported. The etiology of sporadic cases of RSS includes: hypomethylation of IC1 (H19), maternal uniparental disomy (UPD) of chromosome 7, 11p15.5 duplications (rare), and chromosome 7 duplications (rare).

 

CDKN1C variants have recently been identified as a cause of RSS in some families. This test may be considered when results of RSS methylation analysis and UPD 7 studies are negative and there is still a strong clinical suspicion of RSS

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A small percentage of individuals who are carriers or have a diagnosis of Beckwith-Wiedemann syndrome, IMAGe (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies) syndrome, or Russell-Silver syndrome caused by CDKN1C may have a variant that is not identified by this method (eg, large genomic deletions, promoter variants). The absence of a variant, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of Beckwith-Wiedemann syndrome, IMAGe syndrome, or Russell-Silver syndrome. For carrier testing, it is important to first document the presence of a CDKN1C gene variant in an affected family member.

 

In some cases, DNA alterations of undetermined significance may be identified.

Rare variants (ie, polymorphisms) exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. 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

2. DeBaun MR, Niemitz EL, McNeil DE, Brandenburg SA, Lee MP, Feinberg AP: Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. Am J Hum Genet. 2002 Mar;70(3):604-611

3. Choufani S, Shuman C, Weksberg R: Beckwith-Wiedemann syndrome. Am J Med Genet. 2010 Aug;154C(3):343-354

4. Romanelli V, Belinchon A, Benito-Sanz S, et al: CDKN1C (p57[Kip2]) analysis in Beckwith-Wiedemann syndrome (BWS) patients: Genotype-phenotype correlations, novel mutations, and polymorphisms. Am J Med Genet A. 2010 Jun;152A:1390-1397. doi: 10.1002/ajmg.a.33453

5. Lam WWK, Hatada I, Ohishi S, et al: Analysis of germline CDKNIC (p57[Kip2]) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation. J Med Genet. 1999 Jul;36(7):518-523

6. Arboleda VA, Lee H, Parnaik R, et al: Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nat Genet. 2012 May;44(7):788-792

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Bidirectional sequence analysis is performed to test for the presence of a variant in all coding regions and intron/exon boundaries of the CDKN1C gene (excluding c.481-c.595).(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

14 to 20 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole blood: 2 weeks (if available); Extracted DNA: 3 months; Cultured fibroblasts, skin biopsy, amniotic fluid, cultured amniocytes, chorionic villi, cultured chorionic villi: 1 month

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • 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 Regional Manager. For assistance, contact Customer Service.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81479

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

88240-Cryopreservation (if appropriate)

88235-Amniotic fluid culture (if appropriate)

81265-Maternal cell contamination (if appropriate)

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports