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A novel mutation in the SLC40A1 gene associated with reduced iron export in vitro
Author(s) -
MorenoCarralero MaríaIsabel,
MuñozMuñoz JuanAntonio,
CuadradoGrande Nuria,
LópezRodríguez Rafaela,
José HernándezAlfaro María,
delCastilloRueda Alejandro,
EnríquezdeSalamanca Rafael,
Méndez Manuel,
MoránJiménez MaríaJosefa
Publication year - 2014
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23714
Subject(s) - hamp , hepcidin , ferroportin , mutation , penetrance , hemochromatosis , phenotype , gene , biology , genetics , chemistry , iron homeostasis , immunology , inflammation
Ferroportin disease is an inherited disorder of iron metabolism and is caused by mutations in the ferroportin gene ( SLC40A1 ). We present a patient with hyperferritinemia, iron overload in the liver with reticuloendothelial distribution and also in the spleen, and under treatment with erythropheresis. A molecular study of the genes involved in iron metabolism ( HFE, HJV, HAMP, TFR2, SLC40A1 ) was undertaken. In vitro functional studies of the novel mutation found in the SLC40A1 gene was performed. The patient was heterozygous for a novel mutation, c.386T>C (p.L129P) in the SLC40A1 gene; some of his relatives were also heterozygous for this mutation. In vitro functional studies of the L129P mutation on ferroportin showed it impairs its capacity to export iron from cells but does not alter its sensitivity to hepcidin. These findings and the iron overload phenotype of the patient suggest that the novel mutation c.386T>C (p.L129P) in the SLC40A1 gene has incomplete penetrance and causes the classical form of ferroportin disease. Am. J. Hematol. 89:689–694, 2014. © 2014 Wiley Periodicals, Inc.