1. A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene
- Author
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Robert Amson, Adam Telerman, Peter Nielsen, Hermann Heimpel, Carole Beaumont, Bernard Grandchamp, Claire Oudin, Caroline Kannengiesser, Gilles Hetet, Elisabeth Kohne, Christina Balser, Sylvie Rodrigues-Ferreira, Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bichat, Hôpital Bichat - Claude Bernard, Centre Français des Porphyries, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hopital Louis Mourier - AP-HP [Colombes], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Manufacturing Engineering [Aalborg] (M-TECH), Aalborg University [Denmark] (AAU), Medizinische Klinik III, Universitätsklinikum Ulm - University Hospital of Ulm, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hopital Louis Mourier - AP-HP [Colombes]
- Subjects
Male ,Microcytic anemia ,[SDV]Life Sciences [q-bio] ,DNA Mutational Analysis ,Gene Expression ,Cell Cycle Proteins ,medicine.disease_cause ,Biochemistry ,Mice ,0302 clinical medicine ,Child ,Cells, Cultured ,Cell Line, Transformed ,media_common ,Mice, Knockout ,Oncogene Proteins ,Genetics ,Anemia, Hypochromic ,0303 health sciences ,Mutation ,Reverse Transcriptase Polymerase Chain Reaction ,Hematology ,Pedigree ,Codon, Nonsense ,030220 oncology & carcinogenesis ,Female ,Oxidoreductases ,Adolescent ,Anemia ,media_common.quotation_subject ,Blotting, Western ,Immunology ,Nonsense mutation ,Nonsense ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Young Adult ,03 medical and health sciences ,medicine ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,RNA, Messenger ,Allele ,Gene ,030304 developmental biology ,Family Health ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Membrane Proteins ,Cell Biology ,Fibroblasts ,Embryo, Mammalian ,medicine.disease ,Hypochromic anemia ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
STEAP3/TSAP6 encodes a ferrireductase that is involved in the acquisition of iron by developing erythroblasts and steap3/tsap6 null-mice display severe microcytic anemia. We report a family in which 3 siblings born to healthy parents display transfusion-dependent hypochromic anemia. A nonsense STEAP3/TSAP6 was identified in the siblings at the heterozygous state. This mutation was inherited from their father while no mutation was found in their mother. A large variability of expression was found between normal alleles in a control population, confirming a previous report that STEAP3/TSAPS6 is an expressed quantitative trait locus (e-QTL). Determination of the relative allele expression showed that the “normal” allele was expressed at a significantly higher level in the father than in the affected siblings relative to the shared mutated allele. The blood level of STEAP3/TSAP6 mRNA was severely reduced in the siblings, while both parents were in the lower range of normal controls. The STEAP3/TSAP6 protein was also reduced in lymphocytic cell lines from the patients. Collectively, our data support the hypothesis that STEAP3/TSAP6 deficiency leads to severe anemia in the affected siblings and results from the combination of a mutated allele inherited from their father and a weakly expressed allele inherited from their mother.
- Published
- 2011
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