Identification and characterization of the first dmt1 isoform 1a mutation causing a defect in splicing process and an hypomorphic allele expression of dmt1 gene

The human SLC11A2 (DMT1) gene encodes four mRNA transcripts, differing by alternative promoters at 5′ and splicing at 3′ UTR (Fleming et al, 1998; Iolascon & De Falco, 2009). SLC11A2 mutations have been reported in subjects from five unrelated families affected with microcytic anaemia (Mims et al, 2005; Beaumont et al, 2006; Iolascon et al, 2006; Blanco et al, 2009; Bardou-Jacquet et al, 2011). Four of the five cases had a phenotype of microcytic anaemia with increased serum iron and increased transferrin saturation and iron accumulation in the liver (Mims et al, 2005; Beaumont et al, 2006; Iolascon et al, 2006; Bardou-Jacquet et al, 2011) and the mutations affected all SLC11A2 isoforms. To date, no mutations that specifically affect the intestinal SLC11A2 1A isoform have been described.