Basic—Liver, Pancreas, and Biliary TractIdentification of Mutations in SLC40A1 That Affect Ferroportin Function and Phenotype of Human Ferroportin Iron Overload
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Genetic Studies
DNA was extracted from peripheral blood of the patients and unaffected family members. All 8 exons and exon-intron boundaries of SLC40A1 were sequenced in the probands. Samples from family members were evaluated for the presence/absence of mutations identified in probands. A panel of DNA samples from controls was investigated to determine the frequency of novel mutations in the general population. Polymerase chain reaction primers and polymerase chain reaction conditions were as previously
Distinct Phenotypic Presentation of Ferroportin Iron Overload
The index case of family A was a 54-year-old asymptomatic white man who was first referred for further investigation of hyperferritinemia (3015 μg/L) and a transferrin saturation of 21%. At the time of presentation, the patient was in good health; in particular, he had neither joint symptoms nor diabetes. The patient had been successfully treated for ulcerative colitis with mesalazine. His medical history was otherwise unremarkable (Figure 1A).
The index case in family B was a 41-year-old white
Discussion
Here we report on the clinicopathologic manifestations and functional consequences of 2 hitherto unknown human ferroportin variants. It has been proposed that ferroportin iron overload can be readily distinguished from HFE-associated hemochromatosis by a combination of genetic, histologic, and clinical features.1 The genetic characteristics of ferroportin iron overload are its autosomal dominant mode of inheritance and the presence of SLC40A1 mutations, of which 38 distinct variants have so far
Acknowledgments
The authors thank Anna Schlögl, Nadja Baumgartner, and Gisela Egg for excellent technical support.
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the Austrian Science Funds FWF Project P19579 (to H.Z.).