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HelpTest ID UGTK UDP-Glucuronosyl Transferase 1A1 (UGT1A1) Gene, Known Mutation
Useful For
Identifying the presence of a UGT1A1 variant when the variant has been previously identified in a family member (carrier or affected)
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| UGTKM | UGT1A1 Gene, Known Mutation | No | Yes |
| UGTKQ | UGT1A1 Known Mutation Sequencing | No | Yes |
Testing Algorithm
See UGT1A1 Test-Ordering Algorithm in Special Instructions.
Special Instructions
Method Name
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
UGT1A1 Gene, Known MutationSpecimen Type
Whole Blood EDTAContainer/Tube:
Adults: Lavender top (EDTA)
Pediatrics: Purple microtube
Specimen Volume:
Adults: 3 mL
Pediatrics: 1 mL
Collection Instructions:
1. Send specimen in original tube.
2. If submitting microtube, place inside a larger tube or vial for transport.
Forms:
1. UGT1A1 Gene Testing for Hyperbilirubinemia Patient Information Sheet (T664) is required. See 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 (T576) is available in Special Instructions.
Specimen Minimum Volume
0.3 mL
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole Blood EDTA | Ambient (preferred) | |
| Refrigerated | ||
Clinical Information
Excess levels of bilirubin, which is a by-product of heme, have been associated with deleterious health effects. 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 variants in the UGT1A1 gene may cause reduced or absent UGT1A1 enzymatic activity resulting in hyperbilirubinemia.
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) syndrome types I and II are inherited causes of severe unconjugated hyperbilirubinemia. CN type I is associated with the complete absence of UGT1A1 activity and usually presents as intense jaundice in the first days of life and persists thereafter.(3) CN type II is a milder form of hyperbilirubinemia, as compared to CN type I, with at least partial UGT1A1 activity. 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, which is bilirubin-induced brain damage. In addition to phenobarbital, treatments of CN may include: phototherapy, heme oxygenase inhibitors, oral calcium phosphate and carbonate, and liver transplantation.
The UGT1A1 gene maps to chromosome 2q37 and contains 5 exons. This test is intended for analysis of a specific UGT1A1 gene variant or variants that have already been identified in an affected family member. Analysis is performed for the familial variants only.
Reference Values
An interpretive report will be provided.
Cautions
Blood samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic blood or marrow transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient’s genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic blood or marrow transplantation, a pretransplant DNA specimen is recommended for testing.
UGT1A1 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's UGT1A1 status.
This test is for individuals who may harbor a UGT1A1 variant that has been previously identified in the family. If the familial variant is not known, the familial proband should be screened for UGT1A1 variants using UGT2 / UDP-Glucuronosyl Transferase 1A1 (UGT1A1), Full Gene Sequencing, Hyperbilirubinemia.
This assay does not rule out the presence of other variants within this gene. This test is used to detect only known (previously identified) familial variants 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 variants 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.
Day(s) Performed
Tuesday; Varies
Report Available
7 daysPerforming Laboratory
Mayo Medical Laboratories in Rochester
Test Classification
See Individual Test IDsCPT Code Information
81403-Known familial variant not otherwise specified, for gene listed in Tier 1 or Tier 2, DNA sequence analysis, each variant exon