Update on a previously reported missense mutation: The c.1160 C&gt;A mutation in the <i>UGT1A1</i> gene result in Crigler–Najjar syndrome type 1

Variants of the UGT1A1 gene are associated with impaired bilirubin metabolism, which is clinically expressed in Gilbert's syndrome (GS), Crigler-Najjar syndrome types I and II, as well as increased toxicity intaking certain drugs (indinavir, irinotecan, atazanavir, sorafenib, tocilizumab, belinostat, and paracetamol). A common manifestation of these conditions is unconjugated hyperbilirubinemia. The most common variant in the UGT1A1 gene associated with GS (the most common pathology caused by UGT1A1 gene variants) is the UGT1A1*28 variant, which is an increased number of TA repeats in the promoter of the UGT1A1 gene up to 7. However, the UGT1A1*28 variant is not the only gene variant capable of causing unconjugated hyperbilirubinemia. It is known that the variants UGT1A*7, UGT1A*6, and UGT1A*27 were found in the Asian population, which also causes GS with a high frequency. For Caucasians, the UGT1A1*28 variant remains the only common variant that causes GS. At the same time, even the carriage of the UGT1A1*28 variant in the homozygous state does not always lead to the appearance of clinical symptoms. While in the heterozygous form of the UGT1A1*28 variant, high unconjugated hyperbilirubinemia can be observed. Thus, other molecular genetic markers probably explain the incomplete penetrance and variable expressivity of the clinical manifestations of the UGT1A1 gene variants

show abstract

unclassified