Clarke D J, Moghrabi N, Monaghan G, Cassidy A, Boxer M, Hume R, Burchell B
Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Medical School, Scotland, UK.
Clin Chim Acta. 1997 Oct 9;266(1):63-74. doi: 10.1016/s0009-8981(97)00167-8.
Congenital familial non-haemolytic hyperbilirubinaemias are potentially lethal syndromes caused by genetic lesions that reduce or abolish hepatic bilirubin UDP-glucuronosyltransferase activity. Here we describe genetic defects that occur in the UGT1 gene complex that cause three non-haemolytic unconjugated hyperbilirubinaemia syndromes. The most severe syndrome, termed Crigler-Najjar syndrome type I, is mainly associated with mutations in exons 2 to 5 that affect all UGT1 enzymes and many of the mutations result in termination codons and frameshifts. Crigler-Najjar type II syndrome which is treatable with phenobarbital therapy is associated with less dramatic missense mutations or heterozygous expression of mutant and normal alleles. Gilbert's syndrome, the most prevalent (2-19% in population studies) and mildest of the three syndromes is principally caused by a TA insertion at the TATA promoter region upstream of the UGT1A1 exon. Current methods used for the diagnosis and treatment of these diseases are discussed.
先天性家族性非溶血性高胆红素血症是由遗传损伤引起的潜在致命综合征，这些遗传损伤会降低或消除肝脏胆红素UDP - 葡萄糖醛酸基转移酶的活性。在此，我们描述了UGT1基因复合体中发生的导致三种非溶血性非结合性高胆红素血症综合征的遗传缺陷。最严重的综合征，即I型克里格勒 - 纳贾尔综合征，主要与外显子2至5中的突变相关，这些突变影响所有UGT1酶，并且许多突变导致终止密码子和移码。可用苯巴比妥治疗的II型克里格勒 - 纳贾尔综合征与不那么显著的错义突变或突变和正常等位基因的杂合表达相关。吉尔伯特综合征是这三种综合征中最常见的（在人群研究中为2 - 19%）且最轻微的，主要由UGT1A1外显子上游TATA启动子区域的TA插入引起。本文讨论了目前用于这些疾病诊断和治疗的方法。
