Abstract
Iron overload may predominantly involve parenchymal or reticuloendothelial cells, the prototype of parenchymal iron overload being HFE-related genetic haemochromatosis. We studied a family with autosomal dominant hyperferritinaemia in whom the proband showed selective iron accumulation in the Kupffer cells on liver biopsy. Analysis of L and H ferritin genes excluded mutations responsible for hereditary hyperferritinaemia/cataract syndrome or similar translational disorders. Sequence analysis of the ferroportin gene (SLC11A3) in four individuals with hyperferritinaemia singled out a three base pair deletion in a region that contains four TTG repeats. This mutation removes a TTG unit from 780 to 791, and predicts the loss of one of three sequential valine residues 160-162. Denaturing high performance liquid chromatography can be used for its detection. SLC11A3 polymorphism analysis indicates that this probably represents a recurrent mutation due to slippage mispairing. Affected individuals may show marginally low serum iron and transferrin saturation, and young women may have marginally low haemoglobin concentration levels. Serum ferritin levels are directly related to age, but are 10-20 times higher than normal. Heterozygosity for the ferroportin Val 162 deletion represents the prototype of selective reticuloendothelial iron overload, and should be taken into account in the differential diagnosis of hereditary or congenital hyperferritinaemias.
| Original language | English |
|---|---|
| Pages (from-to) | 539-546 |
| Number of pages | 8 |
| Journal | British Journal of Haematology |
| Volume | 119 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2002 |
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Keywords
- Ferritin
- Ferroportin
- Iron
- Iron overload
- Reticuloendothelial cell
ASJC Scopus subject areas
- Hematology
Cite this
Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3). / Cazzola, Mario; Cremonesi, Laura; Papaioannou, Maria; Soriani, Nadia; Kioumi, Anna; Charalambidou, Anastasia; Paroni, Rita; Romtsou, Katerina; Levi, Sonia; Ferrari, Maurizio; Arosio, Paolo; Christakis, John.
In: British Journal of Haematology, Vol. 119, No. 2, 2002, p. 539-546.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3)
AU - Cazzola, Mario
AU - Cremonesi, Laura
AU - Papaioannou, Maria
AU - Soriani, Nadia
AU - Kioumi, Anna
AU - Charalambidou, Anastasia
AU - Paroni, Rita
AU - Romtsou, Katerina
AU - Levi, Sonia
AU - Ferrari, Maurizio
AU - Arosio, Paolo
AU - Christakis, John
PY - 2002
Y1 - 2002
N2 - Iron overload may predominantly involve parenchymal or reticuloendothelial cells, the prototype of parenchymal iron overload being HFE-related genetic haemochromatosis. We studied a family with autosomal dominant hyperferritinaemia in whom the proband showed selective iron accumulation in the Kupffer cells on liver biopsy. Analysis of L and H ferritin genes excluded mutations responsible for hereditary hyperferritinaemia/cataract syndrome or similar translational disorders. Sequence analysis of the ferroportin gene (SLC11A3) in four individuals with hyperferritinaemia singled out a three base pair deletion in a region that contains four TTG repeats. This mutation removes a TTG unit from 780 to 791, and predicts the loss of one of three sequential valine residues 160-162. Denaturing high performance liquid chromatography can be used for its detection. SLC11A3 polymorphism analysis indicates that this probably represents a recurrent mutation due to slippage mispairing. Affected individuals may show marginally low serum iron and transferrin saturation, and young women may have marginally low haemoglobin concentration levels. Serum ferritin levels are directly related to age, but are 10-20 times higher than normal. Heterozygosity for the ferroportin Val 162 deletion represents the prototype of selective reticuloendothelial iron overload, and should be taken into account in the differential diagnosis of hereditary or congenital hyperferritinaemias.
AB - Iron overload may predominantly involve parenchymal or reticuloendothelial cells, the prototype of parenchymal iron overload being HFE-related genetic haemochromatosis. We studied a family with autosomal dominant hyperferritinaemia in whom the proband showed selective iron accumulation in the Kupffer cells on liver biopsy. Analysis of L and H ferritin genes excluded mutations responsible for hereditary hyperferritinaemia/cataract syndrome or similar translational disorders. Sequence analysis of the ferroportin gene (SLC11A3) in four individuals with hyperferritinaemia singled out a three base pair deletion in a region that contains four TTG repeats. This mutation removes a TTG unit from 780 to 791, and predicts the loss of one of three sequential valine residues 160-162. Denaturing high performance liquid chromatography can be used for its detection. SLC11A3 polymorphism analysis indicates that this probably represents a recurrent mutation due to slippage mispairing. Affected individuals may show marginally low serum iron and transferrin saturation, and young women may have marginally low haemoglobin concentration levels. Serum ferritin levels are directly related to age, but are 10-20 times higher than normal. Heterozygosity for the ferroportin Val 162 deletion represents the prototype of selective reticuloendothelial iron overload, and should be taken into account in the differential diagnosis of hereditary or congenital hyperferritinaemias.
KW - Ferritin
KW - Ferroportin
KW - Iron
KW - Iron overload
KW - Reticuloendothelial cell
UR - http://www.scopus.com/inward/record.url?scp=18744400781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18744400781&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2141.2002.03946.x
DO - 10.1046/j.1365-2141.2002.03946.x
M3 - Article
VL - 119
SP - 539
EP - 546
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 2
ER -