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 apla...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.展开更多
基金was supported by grants from the National Natural Science Foundation of China under grant numbers 81770119&81700120。
文摘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.
