Genetic and clinical heterogeneity of ferroportin disease

被引:51
作者
Cemonesi, L
Forni, GL
Soriani, N
Lamagna, M
Fermo, I
Daraio, F
Galli, A
Pietra, D
Malcovati, L
Ferrari, M
Camaschella, C
Cazzola, M
机构
[1] IRCCS, Unit Gen Diagnosis Human Pathol, Milan, Italy
[2] Osped Galliera, Ctr Microcitemia & Anem Congenite, Genoa, Italy
[3] IRCCS, Unit Separat Tech, Milan, Italy
[4] Univ Turin, Dipartimento Sci Clin & Biol, Turin, Italy
[5] Univ Pavia, Dept Hematol, Sch Med, IRCCS,Policlin S Matteo, I-27100 Pavia, Italy
[6] Univ Vita Salute, IRCCS, Milan, Italy
关键词
ferritin; ferroportin; hepcidin; iron; SLC40A1;
D O I
10.1111/j.1365-2141.2005.05815.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Ferroportin is encoded by the SLC40A1 gene and mediates iron export from cells by interacting with hepcidin. SLC40A1 gene mutations are associated with an autosomal type of genetic iron overload described as haemochromatosis type 4, or HFE4 (Online Mendelian Inheritance in Man number 606069), or ferroportin disease. We report three families with this condition caused by novel SLC40A1 mutations. Denaturing high-performance liquid chromatography was employed to scan for the SLC40A1 gene. A D181V (A846T) mutation in exon 6 of the ferroportin gene was detected in the affected members of an Italian family and shown to have a de novo origin in a maternal germinal line. This mutation was associated with both parenchymal and reticuloendothelial iron overload in the liver, and with reduced urinary hepcidin excretion. A G80V (G543T) mutation in exon 3 was found in the affected members of an Italian family With autosomal hyperferritinaemia,. Finally, a G267D (G1104A) mutation was identified in exon 7 in a family of Chinese descent whose members presented with isolated hyperferritinaemia. Ferroportin disease represents a protean genetic condition in which the different SLC40A1 mutations appear to be responsible for phenotypic variability. This condition should be considered not only in families with autosomal iron overload or hyperferritinaemia, but also in cases of unexplained hyperferritinaemia.
引用
收藏
页码:663 / 670
页数:8
相关论文
共 38 条
[11]   Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter [J].
Donovan, A ;
Brownlie, A ;
Zhou, Y ;
Shepard, J ;
Pratt, SJ ;
Moynihan, J ;
Paw, BH ;
Drejer, A ;
Barut, B ;
Zapata, A ;
Law, TC ;
Brugnara, C ;
Kingsley, PD ;
Palis, J ;
Fleming, MD ;
Andrews, NC ;
Zon, LI .
NATURE, 2000, 403 (6771) :776-781
[12]   Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin [J].
Drakesmith, H ;
Schimanski, LM ;
Ormerod, E ;
Merryweather-Clarke, AT ;
Viprakasit, V ;
Edwards, JP ;
Sweetland, E ;
Bastin, JM ;
Cowley, D ;
Chinthammitr, Y ;
Robson, KJH ;
Townsend, ARM .
BLOOD, 2005, 106 (03) :1092-1097
[13]   Ferroportin1 is required for normal iron cycling in zebrafish [J].
Fraenkel, PG ;
Traver, D ;
Donovan, A ;
Zahrieh, D ;
Zon, LI .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (06) :1532-1541
[14]   Ferroportin gene silencing induces iron retention and enhances ferritin synthesis in human macrophages [J].
Gallí, A ;
Bergamaschi, G ;
Recalde, H ;
Biasiotto, G ;
Santambrogio, P ;
Boggi, S ;
Levi, S ;
Arosio, P ;
Cazzola, M .
BRITISH JOURNAL OF HAEMATOLOGY, 2004, 127 (05) :598-603
[15]   Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene [J].
Gordeuk, VR ;
Caleffi, A ;
Corradini, E ;
Ferrara, F ;
Jones, RA ;
Castro, O ;
Onyekwere, O ;
Kittles, R ;
Pignatti, E ;
Montosi, G ;
Garuti, C ;
Gangaidzo, IT ;
Gomo, ZAR ;
Moyo, VM ;
Rouault, TA ;
MacPhail, P ;
Pietrangelo, A .
BLOOD CELLS MOLECULES AND DISEASES, 2003, 31 (03) :299-304
[16]   Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations [J].
Hetet, G ;
Devaux, I ;
Soufir, N ;
Grandchamp, B ;
Beaumont, C .
BLOOD, 2003, 102 (05) :1904-1910
[17]   Novel mutation in ferroportin 1 gene is associated with autosomal dominant iron overload [J].
Jouanolle, AM ;
Douabin-Gicquel, V ;
Halimi, C ;
Loréal, O ;
Fergelot, P ;
Delacour, T ;
de Lajarte-Thirouard, AS ;
Turlin, B ;
Le Gall, JY ;
Cadet, E ;
Rochette, J ;
David, V ;
Brissot, P .
JOURNAL OF HEPATOLOGY, 2003, 39 (02) :286-289
[18]   Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin [J].
Knutson, MD ;
Oukka, M ;
Koss, LM ;
Aydemir, F ;
Wessling-Resnick, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (05) :1324-1328
[19]   Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages [J].
Knutson, MD ;
Vafa, MR ;
Haile, DJ ;
Wessling-Resnick, M .
BLOOD, 2003, 102 (12) :4191-4197
[20]   A novel ferroportin disease in a Japanese patient [J].
Kohgo, Y .
INTERNAL MEDICINE, 2005, 44 (05) :393-394