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Crigler-Najjar Syndrome and Gilbert Syndrome via the UGT1A1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7851 UGT1A1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7851UGT1A181479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Kym Bliven, PhD

Clinical Features and Genetics

Clinical Features

Defects in the UGT1A1 gene can cause both type I and II Crigler-Najjar syndrome (CN1 and CN2) characterized by non-hemolytic unconjugated hyperbilirubinemia (excessive bilirubin in the blood) (Bosma et al. 1992. PubMed ID: 1568736; Ritter et al. 1992. PubMed ID: 1634606; Seppen et al. 1994. PubMed ID: 7989595). Hyperbilirubinemia can cause jaundice (yellowing of the skin and whites of the eyes) and lead to kernicterus (brain damage caused by the accumulation of unconjugated bilirubin in the brain and nerve tissues). In Crigler-Najjar syndrome, jaundice is apparent at birth or in infancy. CN1 is the most severe form with absence of hepatic bilirubin-uridinediphosphoglucuronate (UDP) glucuronosyltransferase (encoded by UGT1A1) activity. CN2 presents with intermediate levels of hyperbilirubinaemia, resulting in an incomplete deficiency of hepatic UGT1A1 activity. UGT1A1 defects can also cause the more common mild hyperbilirubinemia known as Gilbert syndrome (Koiwai et al. 1995. PubMed ID: 8528206; Kadakol et al. 2000. PubMed ID: 11013440), depending on the degree of deficiency of the UDP-glycuronosyltransferase.

Several common polymorphisms in UGT1A1, including the A(TA)7AA allele, have been linked to indirect hyperbilirubinemia with jaundice resulting from adverse drug reactions (for more information, please review Gammal et al. 2016. PubMed ID: 26417955; https://www.pharmgkb.org/gene/PA420). However, this sequencing test has been designed for the molecular diagnosis of patients who present with inherited Crigler-Najjar syndrome or Gilbert syndrome and is not meant to be a pharmacogenetic analysis for this gene, nor has it been designed to help guide dosage requirements. Several common polymorphisms that may affect drug response may not be reported out as part of this test.

Genetics

Crigler-Najjar syndrome types I and II are autosomal recessive disorders caused by defects in the UGT1A1 gene (Bosma et al. 1992. PubMed ID: 1568736; Ritter et al. 1992. PubMed ID: 1634606; Seppen et al. 1994. PubMed ID: 7989595). Gilbert syndrome is generally considered to be an autosomal recessive disorder, but autosomal dominant inheritance has also been suggested (Koiwai et al. 1995. PubMed ID: 8528206; Kadakol et al. 2000. PubMed ID: 11013440). UGT1A1 has five coding exons that encode the UDP-glycuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules such as bilirubin into water-soluble and excretable metabolites. Genetic defects of UGT1A1 include missense, nonsense, splicing variants and small frameshift deletion/insertions (Human Gene Mutation Database). Exon-level large deletions involving UGT1A1 have been also reported, but are uncommon.

Clinical Sensitivity - Sequencing with CNV PG-Select

The detection rate of UGT1A1 pathogenic variants in a cohort of patients with Crigler-Najjar syndrome type I and II or Gilbert syndrome is unknown as only individual cases have been reported.

It is difficult to estimate the exact clinical sensitivity of CNV detection due to the lack of large cohort studies. Large deletions in the UGT1A1 gene have been previously reported, but are uncommon (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the UGT1A1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

The well-known A(TA)nTAA region of the UGT1A1 promoter is also covered in this test.

Several common polymorphisms in UGT1A1, including the A(TA)7AA allele, have been linked to indirect hyperbilirubinemia with jaundice resulting from adverse drug reactions (for more information, please review Gammal et al. 2016. PubMed ID: 26417955; https://www.pharmgkb.org/gene/PA420). However, this sequencing test has been designed for the molecular diagnosis of patients who present with inherited Crigler-Najjar syndrome or Gilbert syndrome and is not meant to be a pharmacogenetic analysis for this gene, nor has it been designed to help guide dosage requirements. Several common polymorphisms that may affect drug response may not be reported out as part of this test.

Indications for Test

Candidates for this test are patients with Crigler-Najjar syndrome (types I and II) or Gilbert syndrome. Testing is also indicated for family members of patients who have known UGT1A1 pathogenic variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in UGT1A1.

Gene

Official Gene Symbol OMIM ID
UGT1A1 191740
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Bosma et al. 1992. PubMed ID: 1568736
  • Gammal et al. 2016. PubMed ID: 26417955
  • Human Gene Mutation Database (Bio-base).
  • Kadakol et al. 2000. PubMed ID: 11013440
  • Koiwai et al. 1995. PubMed ID: 8528206
  • Ritter et al. 1992. PubMed ID: 1634606
  • Seppen et al. 1994. PubMed ID: 7989595

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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