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CLC number: R722

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2014-04-16

Cited: 3

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Citations:  Bibtex RefMan EndNote GB/T7714

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

http://doi.org/10.1631/jzus.B1300233


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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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.

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