JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.5 P.474-481

Two unrelated patients with rare Crigler-Najjar syndrome type I: two novel mutations and a patient with loss of heterozygosity of UGT1A1 gene

Author(s): Yan Li¹, Yu-jin Qu¹, Xue-mei Zhong², Yan-yan Cao¹, Li-min Jin², Jin-li Bai¹, Xin Ma², Yu-wei Jin¹, Hong Wang¹, Yan-ling Zhang², Fang Song¹
Affiliation(s): 1. Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China; more
Corresponding email(s): ylzhang7766@126.com
Key Words: Crigler-Najjar syndrome type I (CN-I), Hyperbilirubinemia, UDP-glycuronosyltransferase gene (UGT1A1), Mutation, Loss of heterozygosity

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Yan Li, Yu-jin Qu, Xue-mei Zhong, Yan-yan Cao, Li-min Jin, Jin-li Bai, Xin Ma, Yu-wei Jin, Hong Wang, Yan-ling Zhang, Fang Song. Two unrelated patients with rare Crigler-Najjar syndrome type I: two novel mutations and a patient with loss of heterozygosity of UGT1A1 gene[J]. Journal of Zhejiang University Science B, 2014, 15(5): 474-481.

@article{title="Two unrelated patients with rare Crigler-Najjar syndrome type I: two novel mutations and a patient with loss of heterozygosity of UGT1A1 gene",
author="Yan Li, Yu-jin Qu, Xue-mei Zhong, Yan-yan Cao, Li-min Jin, Jin-li Bai, Xin Ma, Yu-wei Jin, Hong Wang, Yan-ling Zhang, Fang Song",
journal="Journal of Zhejiang University Science B",
volume="15",
number="5",
pages="474-481",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1300233"
}

%0 Journal Article
%T Two unrelated patients with rare Crigler-Najjar syndrome type I: two novel mutations and a patient with loss of heterozygosity of UGT1A1 gene
%A Yan Li
%A Yu-jin Qu
%A Xue-mei Zhong
%A Yan-yan Cao
%A Li-min Jin
%A Jin-li Bai
%A Xin Ma
%A Yu-wei Jin
%A Hong Wang
%A Yan-ling Zhang
%A Fang Song
%J Journal of Zhejiang University SCIENCE B
%V 15
%N 5
%P 474-481
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300233

TY - JOUR
T1 - Two unrelated patients with rare Crigler-Najjar syndrome type I: two novel mutations and a patient with loss of heterozygosity of UGT1A1 gene
A1 - Yan Li
A1 - Yu-jin Qu
A1 - Xue-mei Zhong
A1 - Yan-yan Cao
A1 - Li-min Jin
A1 - Jin-li Bai
A1 - Xin Ma
A1 - Yu-wei Jin
A1 - Hong Wang
A1 - Yan-ling Zhang
A1 - Fang Song
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 5
SP - 474
EP - 481
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1300233

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: crigler-Najjar syndrome type I (CN-I) is the most severe type of hereditary unconjugated hyperbilirubinemia. It is caused by homozygous or compound heterozygous mutations of the UDP-glycuronosyltransferase gene (UGT1A1) on chromosome 2q37. Two patients clinically diagnosed with CN-I were examined in this paper. We sequenced five exons and their flanking sequences, specifically the promoter region of UGT1A1, of the two patients and their parents. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the UGT1A1 gene copy number of one patient. In patient A, two mutations, c.239_245delCTGTGCC (p.Pro80HisfsX6; had not been reported previously) and c.1156G>T (p.Val386Phe), were identified. In patient B, we found that this patient had lost heterozygosity of the UGT1A1 gene by inheriting a deletion of one allele, and had a novel mutation c.1253delT (p.Met418ArgfsX5) in the other allele. In summary, we detected three UGT1A1 mutations in two CN-I patients: c.239_245delCTGTGCC (p.Pro80HisfsX6), c.1253delT (p.Met418ArgfsX5), and c.1156G>T (p.Val386Phe). The former two mutations are pathogenic; however, the pathogenic mechanism of c.1156G>T (p.Val386Phe) is unknown.

两例罕见I型Crigler-Najjar综合征患者

研究目的：I型Crigler-Najjar综合征（CN-I）为先天性间接胆红素血症的最严重的一种，是由位于染色体2q37的葡萄糖醛酸转移酶基因（UGT1A1）的纯合或复合杂合突变引起的一种罕见的遗传性疾病。本研究对来自两个无关家庭的两例临床诊断为CN-I的患儿及父母进行UGT1A1基因分子遗传学分析。
研究方法：经知情同意后，采集两例患儿及父母外周血；聚合酶链式反应（PCR）扩增UGT1A1基因5个外显子及外显子-内含子交界处，进行测序分析。应用实时定量PCR（qRT-PCR）测定其中一例患者UGT1A1基因的拷贝数。
重要结论：本研究在两例CN-I型患儿中检测到3个UGT1A1基因突变：c.239_245delCTGTGCC (p.Pro80HisfsX6)、c.1253delT (p.Met418ArgfsX5)和c.1156G>T (p.Val386Phe)。前两个突变均为新发的移码突变，预测提前出现终止密码或诱发RNA降解；而突变c.1156G>T (p.Val386Phe)的致病机制尚需进一步研究。

关键词：I型Crigler-Najjar综合征（CN-I）；高胆红素血症；UDP-葡萄糖醛酸转移酶基因（UGT1A1）；突变；杂合性缺失

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两例罕见I型Crigler-Najjar综合征患者

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