title: Rare HFE variants are the most frequent cause of hemochromatosis in non-c282y homozygous patients with hemochromatosis.
abstract: p.Cys282Tyr (C282Y) homozygosity explains most cases of HFE-related hemochromatosis, but a significant number of patients presenting with typical type I hemochromatosis phenotype remain unexplained. We sought to describe the clinical relevance of rare HFE variants in non-C282Y homozygotes. Patients referred for hemochromatosis to the National Reference Centre for Rare Iron Overload Diseases from 2004 to 2010 were studied. Sequencing was performed for coding region and intronic flanking sequences of HFE, HAMP, HFE2, TFR2, and SLC40A1. Nine private HFE variants were identified in 13 of 206 unrelated patients. Among those, five have not been previously described: p.Leu270Argfs*4, p.Ala271Valfs*25, p.Tyr52*, p.Lys166Asn, and p.Asp141Tyr. Our results show that rare HFE variants are identified more frequently than variants in the other genes associated with iron overload. Rare HFE variants are therefore the most frequent cause of hemochromatosis in non-C282Y homozygote HFE patients. Am. J. Hematol. 91:1202-1205, 2016. © 2016 Wiley Periodicals, Inc.
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|Molecular Genetics Department, CHU Rennes, Rennes, 35000, France.
authors: Houda
authors: H
authors: Hamdi-Rozé
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|Molecular Genetics Department, CHU Rennes, Rennes, 35000, France.
authors: Marie-Pascale
authors: MP
authors: Beaumont-Epinette
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|Liver Disease Department, CHU Rennes, Rennes, 35000, France.
authors: Zeineb
authors: Z
authors: Ben Ali
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|Liver Disease Department, CHU Rennes, Rennes, 35000, France.
authors: Caroline
authors: C
authors: Le Lan
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|CHU Limoges Service d'Hépato-gastroentérologie, U850 INSERM Univ Limoges, F-87000, Limoges, France.
authors: Véronique
authors: V
authors: Loustaud-Ratti
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|Hepatology and Gastroenterology department, Regional Hospital of Orléans, Orléans, 45000, France.
authors: Xavier
authors: X
authors: Causse
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|University of Rennes1, Inserm UMR 991, Rennes, 35000, France.
authors: Olivier
authors: O
authors: Loreal
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|Liver Disease Department, CHU Rennes, Rennes, 35000, France.
authors: Yves
authors: Y
authors: Deugnier
authors: University of Rennes1, Inserm UMR 991, Rennes, 35000, France.
authors: Pierre
authors: P
authors: Brissot
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|Molecular Genetics Department, CHU Rennes, Rennes, 35000, France.
authors: Anne-Marie
authors: AM
authors: Jouanolle
authors: CHU Rennes, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.|Liver Disease Department, CHU Rennes, Rennes, 35000, France.|University of Rennes1, Inserm UMR 991, Rennes, 35000, France.
authors: Edouard
authors: 0000-0002-0784-0710
authors: E
authors: Bardou-Jacquet
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D014644:Genetic Variation; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein