A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene.

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.

• Authors: Bernard Grandchamp, Gilles Hetet, Caroline Kannengiesser, Claire Oudin, Carole Beaumont, Sylvie Rodrigues-Ferreira, Robert Amson, Adam Telerman, Peter Nielsen, Elisabeth Kohne, Christina Balser, Hermann Heimpel
• Journal: Blood (Blood) Vol. 118 Issue 25 Pg. 6660-6 (Dec 15 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 22031863 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• Codon, Nonsense
• Membrane Proteins
• Oncogene Proteins
• RNA, Messenger
• Oxidoreductases
• STEAP3 protein, human
• TSAP6 protein, mouse

Topics

• Adolescent
• Anemia, Hypochromic (blood, congenital, genetics)
• Animals
• Blotting, Western
• Cell Cycle Proteins
• Cell Line, Transformed
• Cells, Cultured
• Child
• Codon, Nonsense
• DNA Mutational Analysis
• Embryo, Mammalian (cytology, metabolism)
• Family Health
• Female
• Fibroblasts (cytology, metabolism)
• Gene Expression
• Humans
• Male
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Knockout
• Oncogene Proteins (genetics, metabolism)
• Oxidoreductases
• Pedigree
• RNA, Messenger (blood, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Young Adult