Skip to Content

UGT1A1

UGT1A1 deletion/duplication analysis

Crigler-Najjar syndromes (CN) are inborn disorders of the liver metabolism of bilirubin characterized by non-hemolytic unconjugated hyperbilirubinemia.  CN are classified into two types based on the bilirubin levels, the presence of kernicterus and the reduction of the bilirubin levels upon administration of Phenobarbital or other enzyme-inducing agents.

Mutations in the UGT1A1 gene [OMIM #191740] have been identified in patients with CN. The UGT1A1 gene maps to 2q37.1. It has 4 coding exons, and to date missense, nonsense, frameshift and splice site mutations, and small insertions and deletions have been described.

Deletions and/or duplications involving UGT1A1 as causative of Crigler-Najjar syndrome have been reported.

Read More
UGT1A1 sequencing

Crigler-Najjar syndromes (CN) are inborn disorders of the liver metabolism of bilirubin characterized by non-hemolytic unconjugated hyperbilirubinemia.  CN are classified into two types based on the bilirubin levels, the presence of kernicterus and the reduction of the bilirubin levels upon administration of Phenobarbital or other enzyme-inducing agents.

Mutations in the UGT1A1 gene [OMIM #191740] have been identified in patients with CN. The UGT1A1 gene maps to 2q37.1. It has 4 coding exons, and to date missense, nonsense, frameshift and splice site mutations, and small insertions and deletions have been described

Read More
UGT1A1 genotyping for irinotecan dosing

Irinotecan is an anti-cancer agent that is used for the treatment of metastatic carcinoma of the colon or rectum.  Although it prolongs survival, it causes severe (grade 3-4) diarrhea and neutropenia in approximately 20-35% of patients treated.  The ability to predict patients who will eventually suffer these potentially fatal toxicities is an important consideration when using irinotecan.

Irinotecan is converted in the liver to its active metabolite, SN-38, which subsequently gets conjugated to its glucuronide, SN-38G that is excreted from the body.  UGT1A1 is involved in the glucuronidation of SN-38 to its glucuronide.  Decreased levels of glucuronidation results in elevated amounts of SN-38 that is responsible for the severe diarrhea and neutropenia phenotypes in patients.  Individuals homozygous for the A(TA)7TAA allele are at an elevated risk of developing toxicity phenotypes with irinotecan treatment

Read More
UGT1A1 genotyping for Gilbert syndrome

Gilbert syndrome is characterized by mild, chronic, unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis and is found in approximately 3-10% of the general population.  The diagnosis of this disorder is made on the observation of elevated unconjugated bilirubin levels and normal liver function.  The importance of the diagnosis of this benign syndrome is to rule out more serious liver disease as the underlying cause of the hyperbilirubinemia.

Gilbert syndrome is generally considered to be an autosomal recessive disorder.  However there have been cases of heterozygosity reported in patients with Gilbert syndrome, particularly in the Asian population.  A polymorphism in the promoter region of the UGT1A1 gene, A(TA)7TAA, has been identified in the majority of Caucasian individuals with Gilbert syndrome (80-100%).  A missense change in the UGT1A1 gene, G71R, has been identified in approximately 30-40% of Asian individuals with neonatal hyperbilirubinemia and has been implicated in Gilbert syndrome in this population.  Any samples that are not homozygous for the A(TA)7TAA allele will also be tested for the G71R polymorphism.

Read More
Syndicate content

Forms

In the Spotlight

Newsletter

Join Our Mailing List
Email:
For Email Marketing you can trust