Gene Tested:

UGT1A1

Description

Variants in UGT1A1 cause Crigler-Najjar syndrome (CN), types I and II. CN1 is the more severe form and is characterized by the total absence of hepatic UGT1A1 activity and potentially lethal hyperbilirubinemia with serum bilirubin levels at 20-50mg/dl. CN2 is associated with an incomplete deficiency of hepatic UGT1A1 activity and intermediate levels of hyperbilirubinemia. Variants in UGT1A1 may also cause Gilbert disease, a condition characterized by mild hyperbilirubinemia and possible neonatal jaundice.

Indications

  • Unconjugated hyperbilirubinemia
  • Gilbert syndrome
  • Crigler-Najjar syndrome type 1 or 2

Testing Methodology

Gene Specific Sequencing: PCR-based sequencing of entire coding region, intron/exon boundaries, as well as known pathogenic variants (HGMD 2018.1) in the promoter and deep intronic regions of the specified gene.

Test Sensitivity

Analytical Sensitivity: The sensitivity of DNA sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed.

Limitations: Variants in regulatory regions and non-reported variants in untranslated regions may not be detected by this test. Large deletions involving entire single exons or multiple exons, large insertions and other complex genetic events will not be identified using NGS methodology. Rare primer site variants may lead to erroneous results.

Turnaround Time

28 days

How to Order

Download Heritable Liver Disease requisition. Targeted variant analysis and deletion/duplication analysis is also available for UGT1A1.

References

Canu, G., A. Minucci, et al. (2013) "Gilbert and Crigler Najjar Syndromes: An Update of the UDP-Glucuronosyltransferase 1A1 (UGT1A1) Gene Mutation Database." Blood Cells, Molecules & Diseases 50(4): 273-80.

Chiddarwas, A.S., S.Z. D’Silva, et al. (2017) “Genetic Variations in Bilirubin Metabolism Genes and Their Association with Unconjugated Hyperbilirubinemia in Adults.” Annals of Human Genetics 81:11-19.

Kadakol, A., S.S. Ghosh, et al. (2000) "Genetic Lesions of Bilirubin Uridine-Diphosphoglucuronate Glucuronosyltransferase (UGT1A1) Causing Crigler-Najjar and Gilbert Syndromes: Correlation of Genotype to Phenotype." Human Mutation 16(4): 297-306.

Memon, N., B.I. Weinberger, et al. (2015) "Inherited Disorders of Bilirubin Clearance." Pediatric Research.

Sappal, B.S., S.S. Ghosh, et al. (2002) "A Novel Intronic Mutation Results in the Use of a Cryptic Splice Acceptor Site within the Coding Region of UGT1A1, Causing Crigler-Najjar Syndrome Type 1." Molecular Genetics and Metabolism 75(2): 134-42.

Servedio, V., M. d Apolito, et al. (2005) "Spectrum of UGT1A1 Mutations in Crigler-Najjar (CN) Syndrome Patients: Identification of Twelve Novel Alleles and Genotype-Phenotype Correlation." Human Mutation 25(3): 325.