Gilbert综合征合并骨髓增殖性肿瘤临床特征及基因分析  

Clinical Characteristics and Gene Mutations of Gilbert Syndrome Complicated with Myeloproliferative Neoplasm

作　　者：李星鑫 施均 黄振东 邵英起 聂能 张静[1] 葛美丽 黄金波 郑以州 

机构地区：[1]中国医学科学院、北京协和医学院血液学研究所、血液病医院,天津300020

出　　处：《中国实验血液学杂志》2017年第2期567-571,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金(81470289)

摘　　要：目的:探讨Gilbert综合征合并骨髓增殖性肿瘤(MPN)患者的临床与基因突变特征。方法:采集患者及其儿子外周血样并提取DNA,进行UGT1A1基因全部外显子突变分析。结果:患者白细胞数及血小板数升高,轻度贫血,脾脏肿大,骨髓及其病理活检均提示增生极度活跃,巨核细胞增多,JAK2/V617F阳性;血生化检测显示重度黄疸,以间接胆红素升高为主;UGT1A1基因检测发现1号外显子存在插入突变,由(TA)_6TAA突变到(TA)7TAA,即由野生型UGT1A1*1突变到UGT1A1*28,并发现错义突变c.211G>A,UGT1A1*6杂合,导致葡萄糖醛酸转移酶活性降低;患者及其儿子在启动子及非编码区均存在多态性错义突变,患者儿子不发病。结论:该患者JAK2/V617F+,UGT1A1突变,MPN合并Gilbert综合征的临床表型为国内首次报道,有助于提高血液科医师对Gilbert综合征的认识,有助于黄疸的诊断与鉴别诊断,而基因检测为其确诊手段。Objective： To investigate the clinical characteristics and gene mutations of patients with Gilbert syndrome complicated with myeloproliferative neoplasms （MPN）. Methods： Peripheral blood samples from 1 patient with Gilbert syndrome complicated with MPN and his son were collected to analyse all exon mutations of UGT1A1 gene. Results： The patient with leukocytosis, thrombocythemia, mild anemia and positive JAK2/V617F mutation was initially diagnosed as MPN. The hyperbilirubinemia suggested concurrent disease. Further gene evaluation disclosed a insertion mutation in the （TA）6TAA box, and a missense mutation（G→A） at 211 bp of exon 1, corresponding to the deficiency in the bilirubin-conjugating enzyme uridine-diphosphoglucuronosyl transferaselA1 （UGT1A1）. His son only carried some polymorphism mutation without manifestation of this disease. Conclusion ： It is a first report case of MPN complicated with Gilbert syndrome that can highlight the differential diagnosis for byperbilirubinemia.

关 键 词：骨髓增殖性肿瘤 GILBERT综合征 基因突变 

分 类 号：R555[医药卫生—血液循环系统疾病] R551.3[医药卫生—内科学]