Wilson Disease Known Mutation, ATP7B DNA Sequencing
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Diagnostic confirmation of Wilson disease when familial mutations have been previously identified
Carrier testing of individuals when a mutation in the ATP7B gene has been identified in an affected family member.
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Documentation of the specific familial mutations must be provided with the specimen in order to perform this test.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase chain reaction (PCR)/DNA sequencing are utilized to test for the presence of a specific mutation previously identified in an affected family member.
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Wilson Disease Known Mutation
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
This test can only be performed if a mutation has previously been identified in a family member of this individual.
Specimen must arrive within 96 hours of collection.
Specimen Type: Whole blood
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
1. Invert several times to mix blood.
2. Send specimen in original tube.
Specimen Stability Information: Ambient (preferred)/Refrigerated
1. Molecular Genetics-Congenital Inherited Diseases Patient Information Sheet (Supply T521) in Special Instructions
2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
3. If not ordering electronically, submit a Molecular Genetics Request Form (Supply T245) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Blood: 1 mL
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Wilson disease (WD) is an autosomal recessive disorder that results from the body's inability to excrete excess copper. Typically, the liver releases excess copper into the bile. Individuals with WD lack the necessary enzyme that facilitates clearance of copper from the liver to bile. As a result, copper accumulates first in the liver and gradually in other organs. The brain, kidneys, bones, and corneas can also be affected. WD affects approximately 1 in 30,000 people worldwide, with a carrier frequency of approximately 1 in 90 individuals.
The primary clinical manifestations of WD are hepatic and neurologic. Hepatic disease can be quite variable, ranging from hepatomegaly or other nonspecific symptoms that mimic viral hepatitis to severe liver damage such as cirrhosis. Neurologic symptoms of WD can include poor fine-motor coordination, ataxia, and dysphagia. Psychiatric manifestations are reported in approximately 20% of individuals with WD. A characteristic ophthalmologic finding is the Kayser-Fleischer ring. Individuals with WD typically begin to show symptoms of liver dysfunction or neurologic disease in the first or second decade of life. If not treated, WD can cause liver failure, severe brain damage, and even death.
A variety of laboratory tests are recommended in the initial evaluation for WD. In approximately 95% of cases, serum ceruloplasmin is below normal. Additionally, patients with WD show decreased copper in serum, increased copper in urine, and significantly elevated copper on liver biopsy. While liver biopsy is not recommended as a first-tier screening test for WD, it can be useful to help interpret discrepant biochemical or molecular results. The other tests should be performed prior to sequence analysis of the ATP7B gene, the gene responsible for WD. More than 300 disease-causing mutations have been identified in the ATP7B gene. Most mutations are family-specific with the exception of the H1069Q mutation, which accounts for >50% of identified disease alleles in the Northern European Caucasian population.
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.
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing.
Analysis is performed for the familial mutations provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with Wilson disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Ninety-six normal Caucasian samples were screened for the presence of benign polymorphisms in the ATP7B gene. Selected exons from 21 of these specimens were confirmed by direct sequencing to have at least a single polymorphism. One normal sample was found to be a carrier of an ATP7B mutation (IVS11-2A->G). Five WD patients with known ATP7B mutations were sequenced with 100% concordance.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Roberts EA, Schilsky ML: American Association for Study of Liver Diseases (AASLD): Diagnosis and treatment of Wilson disease: an update. Hepatology 2008;47(6):2089-2111
2. Mak CM, Lam CW: Diagnosis of Wilson's disease: a comprehensive review. Crit Rev Clin Lab Sci 2008;45(3):263-290
Method Description Describes how the test is performed and provides a method-specific reference
DNA sequence analysis is utilized to test for the presence of a specific mutation(s) previously identified in an affected family member.(Gu YH, Kodama H, Du SL, et al: Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease. Clin Genet 2003 Dec;64:479-484)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Friday; 10 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
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
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81403-Known familial variant not otherwise specified, for gene listed in Tier 1 or Tier 2, DNA sequence analysis, each variant exon
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|22700||Reason For Referral||42349-1|