The novel SLC40A1(T419I)variant results in a loss-of-function phenotype and may provide insights into the mechanism of large granular lymphocytic leukemia and pure red cell aplasia  

作　　者：Hongfei Wu Xiang Ren Meili Ge Peiyuan Dong Shichong Wang Huiming Yi Xingxin Li Jiali Huo Xuan Zheng Mengying Gao Jinbo Huang Jing Zhang Min Wang Peng Jin Neng Nie Yingqi Shao Yizhou Zheng 

机构地区：[1]State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China

出　　处：《Blood Science》2022年第1期29-37,共9页血液科学（英文）

基　　金：was supported by grants from the National Natural Science Foundation of China under grant numbers 81770119&81700120。

摘　　要：Variants in the solute carrier family 40 member 1(SLC40A1)gene are the molecular basis of ferroportin disease,which is an autosomal dominant hereditary hemochromatosis.Here,we present a patient with pure red cell aplasia(PRCA)and large granular lymphocytic leukemia(LGLL)associated with an extremely high levels of serum ferritin and iron overload syndrome.Whole exon sequencing revealed a novel heterozygous variant in SLC40A1(p.T419I),which was found in his daughter as well.A series of functional studies in vitro of the T419I variant in ferroportin were conducted and the results revealed a reduced capacity of iron export from cells without changes in protein localization and its sensitivity to hepcidin.Intracellular iron storage in mutated cells was significantly higher than that of wild-type.These findings suggest that the novel variant p.T419I can cause the classical form of ferroportin disease and an elevated intracellular iron level indicates a potential novel pathogenic mechanism underlying PRCA and LGLL.

关 键 词：Ferroportin disease Iron overload Large granular lymphocytic leukemia Pure red cell aplasia SLC40A1 variant 

分 类 号：R73[医药卫生—肿瘤]