Ferroportin Diseases: Functional Studies, a Link Between Genetic and Clinical Phenotype
| Autor: | Yves Deugnier, Martine Ropert, Patricia Leroyer, Lénaïck Détivaud, Caroline Le Lan, Annick Mosser, Véronique David, Pierre Brissot, Edouard Bardou-Jacquet, Olivier Loréal, Marie-Laure Island, Anne-Marie Jouanolle |
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| Přispěvatelé: | Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire de génétique moléculaire, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Centre de référence des surcharges en fer rares d'origine génétique, CHU Pontchaillou [Rennes], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes] |
| Rok vydání: | 2013 |
| Předmět: |
Iron
Mutant Ferroportin Intracellular Space Gene Expression Elevated transferrin saturation Gene mutation medicine.disease_cause hemochromatosis 03 medical and health sciences 0302 clinical medicine Hepcidin Genetics medicine Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology iron overload Cation Transport Proteins SLC40A1 Genetic Association Studies Genetics (clinical) Hemochromatosis ferroportin 030304 developmental biology 0303 health sciences Mutation biology Transferrin saturation Transferrin [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology medicine.disease 3. Good health HEK293 Cells Liver 030220 oncology & carcinogenesis Ferritins biology.protein hepcidin |
| Zdroj: | Human Mutation Human Mutation, Wiley, 2013, 34 (11), pp.1529-36. ⟨10.1002/humu.22396⟩ Human Mutation, 2013, 34 (11), pp.1529-36. ⟨10.1002/humu.22396⟩ |
| ISSN: | 1059-7794 1098-1004 |
| DOI: | 10.1002/humu.22396 |
| Popis: | International audience; Ferroportin (FPN) mediates iron export from cells and this function is modulated by serum hepcidin. Mutations in the FPN gene (SLC40A1) lead to autosomal dominant iron overload diseases related either to loss or to gain of function, and usually characterized by normal or low transferrin saturation versus elevated transferrin saturation, respectively. However, for the same mutation, the phenotypic expression may vary from one patient to another. Using in vitro overexpression of wild-type or mutant FPN proteins, we characterized the functional impact of five recently identified FPN gene mutations regarding FPN localization, cell iron status, and hepcidin sensitivity. Our aim was to integrate functional results and biological findings in probands and relatives. We show that while the p.Arg371Gln (R371Q) mutation had no impact on studied parameters, the p.Trp158Leu (W158L), p.Arg88Gly (R88G), and p.Asn185Asp (N185D) mutations caused an iron export defect and were classified as loss-of-function mutations. The p.Gly204Ser (G204S) mutation induced a gain of FPN function. Functional studies are useful to determine whether or not a FPN gene mutation found in an iron overloaded patient is deleterious and to characterize its biological impact, especially when family studies are not fully informative and/or additional confounding factors may affect bio-clinical expression. |
| Databáze: | OpenAIRE |
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