Crigler-Najjar (CN) disease is caused by a deficiency of the hepatic enzyme, bilirubin UDP-glucuronosyltransferase (B-UGT). We have found two CN type II patients, who were homozygous for a leucine to arginine transition at position 15 of B-UGT1. This mutation is expected to disrupt the hydrophobic core of the signal peptide of B-UGT1. Wild type and mutant B-UGT cDNAs were transfected in COS cells. Mutant and wild type mRNA were formed in equal amounts. The mutant protein was expressed with 0.5% efficiency, as compared to wild type. Mutant and wild type mRNAs were translated in vitro. Wild type transferase is processed by microsomes, no processing of the mutant protein was observed.

Bilirubin, Crigler-Najjar, Endoplasmic reticulum, Signal peptide, UDP-glucuronosyltransferase
dx.doi.org/10.1016/0014-5793(96)00677-1, hdl.handle.net/1765/62037
F E B S Letters
Department of Clinical Genetics

Seppen, J, Steenken, E, Lindhout, D, Bosma, P.J, & Oude Elferink, R.P.J. (1996). A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II. F E B S Letters, 390(3), 294–298. doi:10.1016/0014-5793(96)00677-1