title: [Molecular diagnosis of HFE mutations in routine laboratories. Results of a survey from reference laboratories in France].
abstract: 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.
authors.affiliation: Laboratoire de génétique moléculaire, Centre de référence des surcharges en fer rares d'origine génétique, CHU Pontchaillou, Rennes. anne-marie.jouanolle@chu-rennes.fr
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Jouanolle
authors.forename: Victoria
authors.initials: V
authors.lastname: Gérolami
authors.forename: Cécile
authors.initials: C
authors.lastname: Ged
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Gérald
authors.initials: G
authors.lastname: Le Gac
authors.forename: Serge
authors.initials: S
authors.lastname: Pissard
authors.forename: Jacques
authors.initials: J
authors.lastname: Rochette
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Martinez
mesh_terms: D032962:Consent Forms; D004252:DNA Mutational Analysis / Q000379:methods / Q000592:standards; D003625:Data Collection; D003955:Diagnostic Tests, Routine / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D005602:France; D006432:Hemochromatosis / Q000175:diagnosis* / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007755:Laboratories, Hospital / Q000592:standards / Q000706:statistics & numerical data; D008565:Membrane Proteins / Q000235:genetics*; D025202:Molecular Diagnostic Techniques / Q000379:methods / Q000592:standards; D009154:Mutation / Q000502:physiology; D012015:Reference Standards
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins