EPOR移码突变导致先天性红细胞增多症家系报告并文献复习  

A family report of congenital polycythemia caused by EPOR truncation mutation and literature review

作　　者：韩迎弟 张宇卉 高超[1] 胡耐博 滕广帅[1] 王艳 杜晨霄 陈亚芳 李艳旗 张会勤 彭岚 柳义 白洁 HAN Ying-di;ZHANG Yu-hui;GAO Chao;HU Nai-bo;TENG Guang-shuai;WANG Yan;DU Chen-xiao;CHEN Ya-fang;LI Yan-qi;ZAHNG Hui-qin;PENG Lan;LIU YI;BAI Jie(Department of Hematology,the Second Hospital of Tianjin Medical University,Tianjin 300211,China)

机构地区：[1]天津医科大学第二医院血液科,天津300211

出　　处：《中国实用内科杂志》2022年第7期568-572,共5页Chinese Journal of Practical Internal Medicine

基　　金：国家自然科学基金(82170117)。

摘　　要：目的报道1例携带EPOR移码突变的先天性红细胞增多症(CE)的家系病例,丰富此类疾病的基因突变位点,总结CE患者基本特征,提高对该疾病的认识。方法2019年天津医科大学第二医院分析CE患者的临床特征、实验室特征、内源性红细胞集落(EEC)、促红细胞生成素(EPO)水平及基因测序结果,总结CE患者的诊疗过程,并进行相关文献复习。结果患儿,女性,8岁6个月,“发现红细胞增多5年”,RBC 6.31×10^(12)/L,HGB 186 g/L,HCT 56.4%,EPO水平降低,骨髓EEC培养结果阳性,JAK2^(V617F)、JAK2^(EXON12)基因突变均阴性。EPOR存在1个移码突变,为c.1299_1305del:p.S433fs,口腔黏膜脱落细胞验证为胚系突变,先证者验证发现,突变遗传自其父亲。共检测家系成员21人,发现该家系共12例成员存在EPOR基因同一位点突变。几乎所有存在EPOR基因突变的家系成员的RBC、HGB、HCT高于正常参考范围,但临床症状较轻。结论此类疾病国内报道很少,该家族为国内首次报道EPOR c.1299_1305del:p.S433fs突变的CE患者;该类患者临床症状轻,血常规检查提示RBC增多,HCT增高,血清EPO水平低于正常参考值、EEC阳性,骨髓活检示粒红巨三系增生,诊断时应注意与PV鉴别。Objectives A family case of congenital erythrocytosis(CE)carrying EPOR frameshift mutation was presented.We summarized the basic characteristics of CE patients,and improved the understanding of this disease.Methods The clinical characteristics,laboratory characteristics,EEC,EPO levels and gene sequencing results of CE patients were analyzed,the diagnosis and treatment process of CE patients were summarized,and relevant literature was reviewed in the Second Hospital of Tianjin Medical University in 2019.Results A child,female,8 years and 6 months old,“5 years after discovery of polycytopenia”,RBC 6.31×10^(12)/L,HGB 186 g/L,HCT 56.4%,decreased EPO level,bone marrow EEC culture result was positive.JAK2^(V617F) and JAK2 exon 12 genes were negative.There was a frameshift mutation in EPOR,c.1299_1305del:P.S.433FS,which was verified by oral mucosa cells as germ line mutation.The proband verified that the mutation was inherited from her father.A total of 21 family members were detected and 12 of them were found to have EPOR gene mutation at the same site.The RBC,HGB and HCT of almost all family members with gene mutation were higher than the normal reference range,but the clinical symptoms were mild.Conclusions This kind of disease is rarely reported in China.CE patients of this family are the first with EPOR c.1299_1305Del:P.S433FS mutation reported in China.The clinical symptoms of these patients are mild.Routine blood examination shows increased RBC,increased HCT,lower serum EPO level than normal reference value,positive EEC and bone marrow biopsy showed proliferation of granulocytes,erythrocytes and megakaryocytes.Attention should be paid to distinguish the patients from Polycythemia Vera during diagnosis.

关 键 词：先天性红细胞增多症 EPOR 基因突变 

分 类 号：R555.1[医药卫生—血液循环系统疾病]