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Related Collections Red Cells Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2001, Vol. 97, No. 9, pp. 2555-2560 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS New mutations inactivating transferrin receptor 2 in hemochromatosis type 3 Antonella Roetto, Angela Totaro, Alberto Piperno, Antonio Piga, Filomena Longo, Giovanni Garozzo, Angelita Calì, Marco De Gobbi, Paolo Gasparini, and Clara Camaschella From the Dipartimento di Scienze Cliniche e Biologiche, Azienda Ospedaliera S. Luigi, Orbassano and Dipartimento di Pediatria, OIRM S. Anna, Turin; Servizio di Genetica Medica IRCCS-CSS San Giovanni Rotondo, Foggia; Medicina Interna, Università di Milano Bicocca-Azienda Ospedaliera S. Gerardo, Monza; and Servizio di Immunoematologia e Medicina Trasfusionale, Azienda Ospedaliera "Civile-M. Paternò Arezzo," Ragusa, Italy. Hereditary hemochromatosis usually results from C282Y homozygosity in the HFE gene on chromosome 6p. Recently, a new type of hemochromatosis (HFE3) has been characterized in 2 unrelated Italian families with a disorder linked to 7q. Patients with HFE3 have transferrin receptor 2 (TFR2) inactivated by a homozygous nonsense mutation (Y250X). Here the identification of 2 new TFR2 mutations is reported. In a large inbred family from Campania, a frameshift mutation (84-88 insC) in exon 2 that causes a premature stop codon (E60X) is identified. In a single patient with nonfamilial hemochromatosis, a TA transversion (T515A), which causes a MethionineLysine substitution at position 172 of the protein (M172K), has been characterized. TFR2 gene gives origin to 2 alternatively spliced transcriptsthe -transcript, which may encode a transmembrane protein, and the -transcript, a shorter, possibly intracellular variant. Based on their positions, the effects of the identified mutations on the 2 TFR2 forms are expected to differ. Y250X inactivates both transcripts, whereas E60X inactivates only the -form. M172K has a complex effect: it causes a missense in the -form, but it may also prevent the -form production because it affects its putative initiation codon. Analysis of the clinical phenotype of 13 HFE3 homozygotes characterized at the molecular level has shown a variable severity, from nonexpressing patients to severe clinical complications. The identification of new mutations of TFR2 confirms that this gene is associated with iron overload and offers a tool for molecular diagnosis in patients without HFE mutations. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Pelucchi, R. Mariani, P. Trombini, S. Coletti, M. Pozzi, V. Paolini, D. Barisani, and A. 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