Genetic heterogeneity of Crigler-Najjar syndrome type I: a study of 14 cases.
Genetic heterogeneity of Crigler-Najjar syndrome type I: a study of 14 cases.
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I 型 Crigler-Najjar 综合征的遗传异质性：14 例病例的研究。
DOI：
10.1007/bf00206965
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发表时间：
1994
期刊：
影响因子：
5.3
通讯作者：
Odièvre,M
中科院分区：
文献类型：
--
作者：
Labrune,P;Myara,A;Hadchouel,M;Ronchi,F;Bernard,O;Trivin,F;Chowdhury,NR;Chowdhury,JR;Munnich,A;Odièvre,M
Crigler-Najjar 综合征 I 型 (CN-I) 是一种常染色体隐性遗传疾病，其特征是由于肝脏中胆红素-UDP-葡萄糖醛酸转移酶 (B-UGT) 活性缺乏而导致严重的非结合胆红素血症。两个 B-UGT 由映射到染色体 2q37 的基因复合体 (UGT1) 编码，并且还编码两个苯酚-UDP-葡萄糖醛酸基转移酶。在这里，我们报告了来自不同地理来源的 14 名不相关 CN-I 儿童的 B-UGT1 基因的 11 种突变（包括 9 种新突变）： 法国（7 名患者：A401P、Q357X、W335X、A368T、1223insG、A291V、K426E、K437X）；葡萄牙（两名患者：G308E）；突尼斯（两名患者：Q357R）；土耳其（一名患者：S381R）；意大利（两个兄弟姐妹：S381R）。有趣的是，法国血统的无关先证者携带的 6/14 突变等位基因携带 A401P 突变，表明创始人效应；这种效应可能也存在于葡萄牙、土耳其和突尼斯。由于突变发生在该基因的所有 mRNA 物种共有的外显子 2-5 中，因此在测量这些活性的 5 名患者的肝脏中观察到 B-UGT 和 P-UGT 的联合缺陷。目前的研究证实 CN-I 具有遗传异质性，并表明西欧、中东和北非涉及不同的创始人效应。
Crigler-Najjar syndrome type I (CN-I) is an autosomal recessive condition characterized by severe unconjugated hyperbilirubinemia caused by the lack of bilirubin-UDP-glucuronosyltransferase (B-UGT) activity in the liver. Two B-UGTs are coded for by a gene complex (UGT1) that maps to chromosome 2q37 and that also encodes two phenol-UDP-glucuronosyltransferases. Here, we report eleven mutations (including nine novel mutations) of the B-UGT1 gene in a large series of 14 unrelated CN-I children of various geographic origins: France (seven patients: A401P, Q357X, W335X, A368T, 1223insG, A291V, K426E, K437X); Portugal (two patients: G308E); Tunisia (two patients: Q357R); Turkey (one patient: S381R); Italy (two siblings: S381R). Interestingly, 6/14 mutant alleles carried by unrelated probands of French ancestry bore the A401P mutation, indicating a founder effect; this effect is probably also present in Portugal, Turkey, and Tunisia. Since mutations occurred in exons 2-5 shared by all mRNAs species of the gene, a combined deficiency of B-UGT and P-UGT was observed in the liver of five patients in whom these activities were measured. The present study confirms that CN-I is genetically heterogeneous and suggests that different founder effects are involved in Western Europe, the Middle East, and North Africa.