Molecular Genetic Testing
Familial Nonhemolytic Hyperbilirubinemia (Gilbert`s Syndrome) / Irinotecan Toxicity

Indication and Diagnostic Value

Familial Nonhemolytic Hyperbilirubinemia (Gilbert`s Syndrome):

Congenital nonhemolytic low grade hyperbilirubinemias in patients with Gilbert`s syndrome are linked to mutations in the TATA box upstream of the uridine 5`- diphosphoglucose glucuronosyltransferase (UGT1A1) gene. Contrary to healthy control persons patients are distinguished by the homozygous genotype (TA)(7)TAA with an additional TA-dinucleotide. Carriers of the mutation show lowered enzyme production and consequently decreased enzymatic activity leading to an impaired bilirubin glucuronidation. The homozygous genotype is thus strongly associated with suspected Gilbert`s patients with an prevalence of 5-12% in the european population. However, there also exist other modifying genetic and non-genetic factors that influence the course of the disease.

Irinotecan chemotherapy:

The enzyme UGTA1 plays also an important role in the reaction to drugs with anti-tumor activities because they are mainly conjugated by UGT1A1. Cancer patients often are candidates for irinotecan chemotherapy. In particular, the (TA)(7)TAA genotype predicts severe toxicity by irinotecan in cancer patients. Therefore, the genetic test is clinically helpful for predicting severe side effects and toxicity.

Samples and Test Method

IMMD blood stain test paper is required.
By using PCR and fragment analysis on an ABI sequencing device the test unambiguously identifies the sequence variants in the promoter of the UGT1A1 gene. The specificity of the diagnosis reaches almost 100%.

Turnaround time is 14 days.

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