Author(s) : Anne-Marie Jouanolle, Victoria Gérolami, Cécile Ged, Bernard Grandchamp, Gérald Le Gac, Serge Pissard, Jacques Rochette, Patricia Aguilar-Martinez, Laboratoire de génétique moléculaire, Centre de référence des surcharges en fer rares d’origine génétique, CHU Pontchaillou, Rennes, Laboratoire de biologie moléculaire, CHU Conception, Marseille, Laboratoire de biochimie, CHU Bordeaux, Hôpital Pellegrin, Inserm U1035 Université V Segalen Bordeaux 2, Bordeaux, Service de génétique APHP, Université Denis Diderot, CHU Xavier Bichat, Paris, Laboratoire de génétique moléculaire et d’histocompatibilité, CHRU de Brest - Hôpital Morvan, Université de Bretagne Occidentale, Inserm U613, Brest, Laboratoire de biochimie et de génétique, GH Henri Mondor-Chenevier, UPEC (Université Paris Est Créteil), Créteil, Laboratoire de génétique moléculaire, Inserm U 925, CHU d’Amiens, Laboratoire d’hématologie, Hôpital Saint Eloi, CHU de Montpellier.
Summary :HFE-related hemochromatosis (HFE hemochromatosis) or type 1 hemochromatosis is an autosomal recessive disease characterized by progressive iron overload usually expressed in adulthood. The
HFE gene, located on the short arm of chromosome 6 (6p21.3), encodes a protein that plays a crucial role in iron metabolism by modulating hepcidin synthesis in the liver. Homozygosity for the p.Cys282Tyr mutation accounts for nearly 80% of cases of hemochromatosis in France. Genetic testing is the key investigation to confirm the diagnosis of HFE hemochromatosis. A survey on routine practices was carried out among the eight reference laboratories of the French national network on genetic iron disorders. The main findings from this survey are as follows: 1) the p.Cys282Tyr mutation must be searched for as an initial step to establish the diagnosis of HFE hemochromatosis. This is in agreement with the recommendations of the French Health Authority (HAS) published in 2005. In these recommendations, homozygosity for the p.Cys282Tyr mutation with at least elevated transferrin saturation, is considered the only genotype that confirms of the diagnosis of HFE hemochromatosis\; 2) in combination with the p.Cys282Tyr mutation (compound heterozygous genotypes), the p.Ser65Cys and the p.His63Asp variants may contribute to the occurrence of mild iron overload\; 3) family screening is mandatory following the detection of homozygous individuals for the p.Cys282Tyr mutation.
Keywords : hemochromatosis, HFE, diagnosis, mutation, iron
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Figure 1 Exemple de consentement pour examen des
caractéristiques génétiques d’un individu (test HFE).
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