Gilbert综合征合并骨髓增殖性肿瘤临床特征及基因分析

发布时间：2018-06-24 16:53

本文选题：骨髓增殖性肿瘤 + Gilbert综合征　；参考：《中国实验血液学杂志》2017年02期

【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.211GA,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。
[Abstract]:Objective: to investigate the clinical and gene mutation characteristics of patients with Gilbert syndrome complicated with bone marrow proliferative tumor (MPN). Methods: the peripheral blood samples of patients and their sons were collected and DNA was extracted, and all exon mutations of UGT1A1 gene were analyzed. Results: the white blood cell count and platelet count increased, mild anemia, splenomegaly, bone marrow and pathological biopsy all showed hyperplastic activity, megakaryocyte proliferation and JAK2 / V617F positive, blood biochemical examination showed severe jaundice. UGT1A1 gene was detected mainly by indirect bilirubin increase. The insertion mutation of exon 1 was found, from (TA) 6TAA to (TA) 7TAA, that is, from wild type UGT1A1A1t1 to UGT1A1O28, and the missense mutation c.211GAUGT1A16 heterozyme was found, which resulted in the decrease of glucuronyltransferase activity. The patients and their sons had polymorphic missense mutations in promoter and non-coding regions. Conclusion: the clinical phenotype of JAK2 / V617F UGT1A1 mutation MPN combined with Gilbert syndrome is reported for the first time in China, which is helpful to improve the understanding of Gilbert syndrome among hematologists, to diagnose and differentiate jaundice, and to diagnose jaundice by gene test.
【作者单位】：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;
【基金】：国家自然科学基金(81470289)
【分类号】：R733.3;R575

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