Identification and characterization of the first SLC11A2 isoform 1a mutation causing a defect in splicing process and an hypomorphic allele expression of the SLC11A2 gene.

The human SLC11A2 (DMT1) gene encodes four mRNA transcripts,differing by alternative promoters at 5′ and splicing at3′ UTR. SLC11A2 mutations have been reported in subjects fromfive unrelated families affected with microcytic anaemia. Four ofthe five cases had a phenotype of microcytic anaemia withincreased serum iron and increased transferrin saturationand iron accumulation in the liver and the mutations affected all SLC11A2 isoforms.The novel SLC11A2 mutation described, causes an abnormal splicing in intestinalcells with a consequent local reduction of SLC11A2 proteinand a defect in SLC11A2 expression in erythroid cells thatimpairs haemoglobin production.