SNP Shot: Genomic Insights

Gilbert syndrome is a mild condition marked by intermittent increases in bilirubin, a potentially harmful substance, in the bloodstream (hyperbilirubinemia). Bilirubin, a byproduct of red blood cell breakdown with a yellowish-orange color, must be processed by the liver to be eliminated from the body. The liver transforms the toxic form of bilirubin (unconjugated bilirubin) into a harmless form (conjugated bilirubin). Individuals with Gilbert syndrome experience an accumulation of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia). Bilirubin levels in those affected are variable and rarely reach levels high enough to cause jaundice, a yellowing of the skin and eyes.

Gilbert syndrome is usually diagnosed during adolescence. Hyperbilirubinemia episodes in individuals with the condition are usually minor and often triggered by stress factors such as dehydration, fasting, illness, intense physical activity, or menstruation. Some individuals may also experience abdominal pain or fatigue. However, around 30% of people with Gilbert syndrome show no symptoms and are diagnosed incidentally through routine blood tests that reveal elevated unconjugated bilirubin.

Inheritance:

Gilbert syndrome can be inherited in different ways. When caused by the UGT1A1*28 variant in the UGT1A1 gene's promoter region, it follows an autosomal recessive inheritance pattern. This means that both copies of the gene in each cell must carry the mutation for the condition to manifest. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but usually do not display any signs or symptoms of the condition. In cases where the condition is caused by a missense mutation within the UGT1A1 gene, it is inherited in an autosomal dominant pattern, meaning that only one copy of the altered gene in each cell is sufficient to cause the disorder. A more serious condition, Crigler-Najjar syndrome, arises when both copies of the UGT1A1 gene contain mutations.