Gilbert综合征合并骨髓增殖性肿瘤临床特征及基因分析

摘要

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 transferase1 A1 (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 hyperbilirubinemia.%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.