ANALYSIS OF BILIRUBIN URIDINE 5'-DIPHOSPHATE IN (UDP)-GLUCURONOSYLTRANSFERASE GENE-MUTATIONS IN 7 PATIENTS WITH CRIGLER-NAJJAR-SYNDROME TYPE-II

Crigler-Najjar syndrome (CN) type II is caused by a reduction in hepat ic bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase acti vity. Recently, there has been progress in mutation analysis of patien ts with CN type II. Here, we analyzed both the coding and the promoter regions of the gene in seven Japanese patients with CN type II from f ive unrelated families. The mutations found in this study were classif ied into three types. The first type was composed of double homozygous missense mutations (Gly71Arg and Tyr486Asp) in exons 1 and 5. These m utations, which were detected in five patients from three unrelated fa milies, were the commonest. The second type, which was detected in one patient, consisted of a single homozygous missense mutation (Arg209Tr p) in exon 1. The third type, which was detected in one patient and wa s a new type of mutation combination, was composed of a homozygous ins ertion mutation of the TATAA element and a heterozygous missense mutat ion (Pro229Gln) in exon 1. Although the first and the second type of m utations are recessive, the third type appears to be dominant with inc omplete penetrance, since the allele frequency of the insertion mutati on of the TATAA element is very high (40%).