1例UGT1A1基因双纯合突变患者的Crigler-Najjar综合征2型合并胆囊炎

IF 3.5 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Jianhui Zhang, Rongrong Chen, Xiang Chen, Ying Chen, Qilin Chen, Shiyun Lu, Jiewei Luo, Xiaoling Zheng, Mengshi Chen
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引用次数: 0

摘要

Crigler-Najjar综合征(CNS)和Gilbert综合征(GS);OMIM: 143500)是罕见的常染色体隐性遗传病,由于UGT1A1酶活性降低而引起非共轭高胆红素血症。Crigler-Najjar综合征2型(CNS2;OMIM: 606785)增加胆囊结石形成和胆囊炎的风险,而GS很少引起健康问题。我们发现一个28岁的男性患者反复右上腹部疼痛,经历了持续黄疸从出生。基因检测发现UGT1A1基因存在罕见的双纯合突变A(TA)7TAA (rs3064744)和P229Q (rs35350960),诊断为胆囊结石和胆囊炎。经系谱调查,我们发现胆红素轻度升高的患者父母有复合杂合突变A(TA)7TAA和P229Q,为GS。生物信息学分析表明,A(TA)7TAA位于基因UGT1A1启动子的TATA-box区域,影响基因转录起始,而P229Q修饰蛋白质三维结构,可能有害。在这个家系中,双纯合突变比复合杂合突变具有更严重的表型。排除胆道梗阻后,应怀疑遗传原因导致的高胆红素血症,早期胆红素降低(< 103µmol/L (6 mg/dL))可能降低CNS2患者胆囊炎等并发症的风险,但需要进一步的长期随访研究来证实这一观察结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Crigler-Najjar syndrome type 2 complicating cholecystitis in a patient with UGT1A1 gene double homozygous mutations.

Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)7TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)7TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)7TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.

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来源期刊
Frontiers of Medicine
Frontiers of Medicine ONCOLOGYMEDICINE, RESEARCH & EXPERIMENTAL&-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
18.30
自引率
0.00%
发文量
800
期刊介绍: Frontiers of Medicine is an international general medical journal sponsored by the Ministry of Education of China. The journal is jointly published by the Higher Education Press and Springer. Since the first issue of 2010, this journal has been indexed in PubMed/MEDLINE. Frontiers of Medicine is dedicated to publishing original research and review articles on the latest advances in clinical and basic medicine with a focus on epidemiology, traditional Chinese medicine, translational research, healthcare, public health and health policies.
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