UDP-Glucuronosyl Transferase 1A1 (UGT1A1) Gene, Known Mutation
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Identifying the presence of a UGT1A1 mutation when the mutation has been identified in a family member (carrier or affected)
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
|Test ID||Reporting Name||Available Separately||Always Performed|
|UGTKM||UGT1A1 Gene, Known Mutation||No||Yes|
|UGTKQ||UGT1A1 Known Mutation Sequencing||No||Yes|
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
See UGT1A1 Test-Ordering Algorithm in Special Instructions.
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) Followed by Site-Specific Gene Sequencing Analysis
(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
UGT1A1 Gene, Known Mutation
Uracil Glucuronyl transferase
Uridine Diphosphate Glucosyltransferase 1
Uracil Glucuronyl transferase
Uridine Diphosphate Glucosyltransferase 1
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
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.
Multiple whole blood EDTA genotype tests can be performed on a single specimen after a single extraction. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Adults: Lavender top (EDTA)
Pediatrics: Purple microtube
Adults: 3 mL
Pediatrics: 1 mL
1. Send specimen in original tube.
2. If submitting microtube, place inside a larger tube or vial for transport.
1. Bone marrow and liver transplants will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions.
2. Transfusions will interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
1. UGT1A1 Gene Testing for Hyperbilirubinemia Patient Information Sheet (Supply T664) 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.
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.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Ambient (preferred)|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Bilirubin, resulting from the breakdown of heme, is a water-insoluble toxic compound. Uridine diphosphate (UDP)-glucuronosyl transferase 1A1 (UGT1A1) is responsible for bilirubin conjugation with glucuronic acid. This renders the bilirubin water soluble and permits excretion of the bilirubin-glucuronide conjugates in urine.(1) Genetic mutations in the UGT1A1 gene may cause reduced or absent UGT1A1 enzymatic activity resulting in hyperbilirubinemia (eg, Gilbert syndrome, Crigler-Najjar syndrome).
Gilbert syndrome, found in 5% to 10% of the population, is the most common hereditary cause of increased bilirubin and is associated with mild hyperbilirubinemia (bilirubin levels are typically around 3 mg/dL.(2) Gilbert syndrome is caused by a 25% to 50% reduced glucuronidation activity of the UGT1A1 enzyme and characterized by episodes of mild intermittent jaundice and the absence of liver disease.
Crigler-Najjar (CN) types I and II are inherited causes of severe unconjugated hyperbilirubinemia. CN type I is associated with no UGT1A1 enzymatic activity and usually presents as intense jaundice in the first days of life and persists thereafter.(3) Type II is a milder form in which bilirubin levels are <20 mg/dL. Phenobarbital, a drug that induces synthesis of a number of hepatic enzymes, is effective in decreasing serum bilirubin levels by approximately 25% in patients with CN type II; CN type I does not respond to phenobarbital treatment.
If left untreated, the buildup of bilirubin in a newborn can cause kernicterus, bilirubin-induced brain damage. Treatments of CN include: phototherapy, heme oxygenase inhibitors, oral calcium phosphate and carbonate, and liver transplantation. Phototherapy becomes ineffective at later ages and liver transplantation should occur prior to the onset of brain damage (before phototherapy becomes ineffective).
The UGT1A1 gene maps to chromosome 2q37 and contains 5 exons. Currently, there are more than 130 known mutations in UGT1A1, with 45 mutations that cause a decrease in UGT1A1 enzyme activity. Analysis is performed for the familial mutation only.
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
This test is for individuals who are at risk for a UGT1A1 mutation that has been previously identified in the family. If the familial mutation is not known, the familial proband should be screened for a UGT1A1 mutation using UGT2 / UDP-Glucuronosyl Transferase 1A1 (UGT1A1), Full Gene Sequencing, Hyperbilirubinemia.
This assay does not rule out the presence of other mutations within this gene. This test can only be used for known mutations occurring in the promoter, exons, exon-intro boundaries, and the region in the distal promoter called the "phenobarbital response enhancer module."
An alternative splice site for exon 5 (referred to as exon 5b) has been discovered and described in the literature. This new exon is described to have a decrease in enzymatic activity (compared with exon 5a: previously known as exon 5), but little is known about the frequency of exon 5b or how it impacts hyperbilirubinemia. Currently, we are not testing or sequencing exon 5b; we continue to monitor the literature for new information on exon 5b.
Rare 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.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Guilemette C: Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenomics J 2003;3:136-158
2. Innocenti F, Grimsley C, Das S, et al: Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groups. Pharmacogenetics 2002;12:725-733
3. Costa E, Vieira E, Martins M, et al: Analysis of the UDP-glucuronosyltransferase gene in Portuguese patients with a clinical diagnosis of Gilbert and Crigler-Najjar syndromes. Blood Cells Mol Dis 2006;36:91-97
4. Kitagawa C, Ando M, Ando Y, et al: Genetic polymorphism in the Phenobarbital- responsive enhancer module of the UDP-glucuronosyltransferase 1A1 gene and irinotecan toxicity. Pharmacogenet Genomics 2005;15:35-41
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood. The UGT1A1 gene is amplified by PCR. The PCR product is then purified and sequenced in both directions using fluorescent dye-terminator chemistry. Sequencing products are separated on an automated sequencer and trace files analyzed for variations in the region of the gene containing the suspected familial mutation using mutation detection software and visual inspection.(Unpublished Mayo method)
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.
Monday through Friday; Varies
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 Extracted DNA: 2 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|
|UGTKQ||UGT1A1 Known Mutation Sequencing||In Process|
|89396||UGT1A1 Gene, Known Mutation||In Process|
|30988||UGT1A1 Gene, Known Mutation Interp||69047-9|