A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene.
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A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene. / Grandchamp, Bernard; Hetet, Gilles; Kannengiesser, Caroline; Oudin, Claire; Beaumont, Carole; Rodrigues-Ferreira, Sylvie; Amson, Robert; Telerman, Adam; Nielsen, Peter; Kohne, Elisabeth; Balser, Christina; Heimpel, Hermann.
in: BLOOD, Jahrgang 118, Nr. 25, 25, 2011, S. 6660-6666.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene.
AU - Grandchamp, Bernard
AU - Hetet, Gilles
AU - Kannengiesser, Caroline
AU - Oudin, Claire
AU - Beaumont, Carole
AU - Rodrigues-Ferreira, Sylvie
AU - Amson, Robert
AU - Telerman, Adam
AU - Nielsen, Peter
AU - Kohne, Elisabeth
AU - Balser, Christina
AU - Heimpel, Hermann
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Adolescent
KW - Young Adult
KW - Child
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - DNA Mutational Analysis
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Gene Expression
KW - Pedigree
KW - Family Health
KW - Blotting, Western
KW - Codon, Nonsense
KW - Fibroblasts/cytology/metabolism
KW - Cell Line, Transformed
KW - Membrane Proteins/genetics/metabolism
KW - Anemia, Hypochromic/blood/congenital/genetics
KW - Embryo, Mammalian/cytology/metabolism
KW - Oncogene Proteins/genetics/metabolism
KW - RNA, Messenger/blood/genetics
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Adolescent
KW - Young Adult
KW - Child
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - DNA Mutational Analysis
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Gene Expression
KW - Pedigree
KW - Family Health
KW - Blotting, Western
KW - Codon, Nonsense
KW - Fibroblasts/cytology/metabolism
KW - Cell Line, Transformed
KW - Membrane Proteins/genetics/metabolism
KW - Anemia, Hypochromic/blood/congenital/genetics
KW - Embryo, Mammalian/cytology/metabolism
KW - Oncogene Proteins/genetics/metabolism
KW - RNA, Messenger/blood/genetics
M3 - SCORING: Journal article
VL - 118
SP - 6660
EP - 6666
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 25
M1 - 25
ER -