Analysis of the (TA)n-repeats region in the UGT1A1 gene promoter (c.-55_-54insTA mutation) - diagnostics of Gilbert's syndrome

Gilbert syndrome is a common genetic disorder, in European populations European populations it affects about 10-15% of people. It belongs to the fluke of jaundice congenital with a mild course. The cause of the disease is a decrease in the activity of the enzyme responsible for glucuronidation of bilirubin in the liver by about 70%, which reduces the proportion of bound bilirubin in the bile well below the typical value of 90%.
The disease is caused by a mutation of the gene uridine-5'-diphosphoglucose-glucuronosyltransferase of bilirubin (UGT1A1) on chromosome 2q37. There is a common repetitive mutation that increases the number of TA dinucleotide repeats from 6 to 7 Inheritance is recessive. Patients sometimes exhibit increased and prolonged neonatal jaundice. Typically, the disease is diagnosed between 15 and 30 years of age, and manifests with recurrent mild jaundice induced by starvation, dehydration, fever, certain medications, surgery, excessive exercise exercise or menstruation.
Characteristically, there is an elevated level of unbound bilirubin and a rapid reduction in bilirubin levels after phenobarbital, the level of bilirubin in the blood ranges from 17 to 50 μmol/L. In general, there are no clinical symptoms, sometimes abdominal pain, a feeling of fullness in the epigastrium, vomiting and intolerance of fatty foods.
Gilbert syndrome can significantly aggravate the course of diseases such as glucose-6-phosphate deficiency,beta-thalassemia, hereditary spherocytosis, cystic fibrosis.

The indication for the test is the diagnosis of cases of prolonged neonatal jaundice; diagnosis of cases of jaundice in adolescence or adulthood, with predominance of bilirubin unbound with normal levels of liver enzymes and absence of hemolysis, especially recurrent after fever, dehydration, starvation, etc.; differential diagnosis of jaundice with predominance of unbound bilirubin or excessive hemolysis (including deficiency of glucose-6-phosphate, beta-thalassemia, hereditary spherocytosis); familial testing: detection of UGT1A1 gene mutations in a relative in families with chronic and recurrent jaundice; planned use of irinotecan in therapy or side effects after drugs metabolized by glucuronidation.