成年发病戈谢病1例临床特征及家系基因突变分析  

Clinical characteristics and family genetic mutation analysis of adult onset Gaucher disease:reportof1case

作　　者：施杰 徐宁 田野 牛艳 贾思寻 杨晨萌 方美云 Shi Jie;Xu Ning;Tian Ye;Niu Yan;Jia Sixun;Yang Chenmeng;Fang Meiyun(Department of Hematology,Affiliated Zhongshan Hospital of Dalian University,Dalian 116000,China;Department of Oncology,Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China)

机构地区：[1]大连大学附属中山医院血液科,大连116000 [2]陕西中医药大学附属医院肿瘤科,咸阳712000

出　　处：《白血病．淋巴瘤》2024年第8期472-475,共4页Journal of Leukemia & Lymphoma

摘　　要：目的探讨成年发病戈谢病患者的临床特征和家系基因突变结果。方法回顾性分析2020年3月大连大学附属中山医院收治的1例戈谢病患者的诊治经过, 并进行文献复习。结果患者(先证者)女性, 34岁, 2005年发现贫血及血小板计数低、脾大, 此后定期体检白细胞、红细胞、血小板三系减少渐进加重, 脾脏进行性大, 因乏力加重于2020年3月19日就诊。查体示肝脾大, 血常规示三系减少, 骨髓形态学见大量戈谢细胞。先证者外周血β-葡萄糖脑苷脂酶(GBA)1.8 nmol·mg-1·h-1(参考值10~25 nmol·mg-1·h-1), 其父、母、弟弟、女儿β-GBA均正常。二代测序结果示, 先证者BCL2基因突变, 位点c.127G>A p.A43T, 突变频率49.53%。GBA基因检测示, 先证者c.1448T>C杂合突变(致病突变), c.1026A>G和c.1038C>T杂合突变(同义突变), c.1075G>T杂合突变(临床意义不明突变);先证者父亲c.1448T>C杂合突变, 为携带者;先证者母亲c.1075G>T杂合突变;先证者弟弟未发现基因突变;先证者女儿c.1448T>C杂合突变, 为携带者。诊断为戈谢病Ⅰ型(非神经病变型)。患者拟参加伊米苷酶临床试验, 随访中, 血常规三系相对稳定, 脾脏仍进行性增大。结论戈谢病属于罕见病, 易误诊、漏诊, 当有患者不明原因血细胞减少、肝脾大并且多脏器受累时, 需警惕戈谢病的可能性, 应尽早完善酶学及基因检查。Objective To investigate the clinical features and family gene mutation results of the adult onset Gaucher disease patient.Methods The diagnosis and treatment of a patient with Gaucher disease who was admitted to the Affiliated Zhongshan Hospital of Dalian University in March 2020 were retrospectively analyzed,and the literature was reviewed.Results The patient(the proband)was a 34-year-old female,the anemia,thrombocytopenia and splenomegalia were found in 2005.After regular physical examination,the decrease of leukocyte,red blood cell and platelet was gradually aggravated,and the progressive enlargement of the spleen was aggravated.She visited the clinic on March 19,2020 due to worsening of fatigue.The physical examination revealed hepatomegaly,splenomegaly;blood routine examination showed pancytopenia,and bone marrow morphology showed a large number of Gaucher cells.Peripheral bloodβ-glucocerebrosidase(GBA)of the proband was 1.8 nmol·mg^(-1)·h^(-1)(reference value 10-25 nmol·mg^(-1)·h^(-1)),and the GBA of her father,mother,brother,and daughter was normal.The second-generation sequencing results showed that the proband had a mutation in the BCL2 gene at locus c.127G>A p.A43T,with a mutation frequency of 49.53%.GBA gene testing showed that the proband had a heterozygous mutation at c.1448T>C(a pathogenic mutation),heterozygous mutations at c.1026A>G and c.1038C>T(homozygous mutations),and a heterozygous mutation at c.1075G>T(mutation of unknown clinical significance).The proband's father had c.1448T>C heterozygous mutation,and he was a carrier;the proband's mother had c.1075G>T heterozygous mutation;the proband's brother had no gene mutation;the proband's daughter had c.1448T>C heterozygous mutation,and she was a carrier.The diagnosis was type I Gaucher disease(non-neuropathic).The patient was proposed to participate in the clinical trial of imiglucerase,and during the follow-up,the blood routine was relatively stable,and the spleen remained progressively enlarged.Conclusions Gaucher disease is rare,which is

关 键 词：戈谢病 系谱 二代测序 

分 类 号：R596[医药卫生—内科学]