What we know so far
The genetic background in patients with Gilbert syndrome involves the promotor region of UGT1A1 gene. The syndrome manifests only in people who are homozygous for the variant promoter. As a result, its inheritance is most consistent with an autosomal recessive trait. In addition, heterozygotes for the Gilbert genotype have higher average plasma bilirubin concentrations compared with those with two wild-type alleles.
The mutation responsible for Gilbert syndrome is in the promoter region, upstream to exon 1 of UGT1A1. The defect in Gilbert syndrome is different from that in the Crigler-Najjar syndromes, in which bilirubin-UGT is either absent or produced in an abnormal form with reduced or no activity.
Other factors are probably involved in the expression of the Gilbert phenotype. For example, in the Japanese population, other mutations within the coding regions of UGT1A1 can cause the Gilbert phenotype.
There is a high chance that some heterozygous carriers of structural mutations that cause Crigler-Najjar syndrome type also carry the Gilbert type of TATAA element on their normal allele. Such combined defects can lead to severe hyperbilirubinemia. This is why some family members of patients with Crigler-Najjar syndrome have intermediate levels of hyperbilirubinemia.