Impact of HFE-2 and HAMP Gene Variations on Iron Overload in Pediatric Patients with Non-Transfusion Dependent Thalassemia: A Pilot Study

Patients with non-transfusion dependent thalassemia (NTDT) develop variable degrees of iron overload. Possible genes which may be implicated in causing iron overload are hepcidin (HAMP) and hemojuvelin (HFE). There is variable data assessing the role of c.-582Y A > G HAMP gene and H63D hotspot in HFE-1 gene in causing iron overload, while role of HFE-2 gene is undetermined. Twenty-five patients with NTDT (>= 10 years) were assessed for iron overload. Genetic analysis for beta-globin, alpha-globin, HAMP, HFE-2 and C282Y and H63D hotspots in HFE-1 genes was performed. T2*MRI demonstrated elevated LIC in 48% patients. No mutations were detected in HAMP gene or HFE-1 hotspots. Four single nucleotide variations (SNV) were detected in HFE-2 gene in 4 (20%) patients, including a novel SNV, p.Gln315Arg in 2 patients in heterozygous state. This is a likely pathogenic mutation; however, in heterozygous state, it did not lead to iron overload. HAMP and HFE-2 gene variations were infrequently seen in this pilot study, with no significant impact on iron overload. Presence of SNV p.Gln315Argin HFE-2 gene needs to be evaluated in larger sample sizes in our population to determine the incidence in homozygous state and its association with iron overload.

Automated summary

This study found no mutations in the HAMP gene or HFE-1 hotspots in NTDT patients, but detected single nucleotide variations in the HFE-2 gene in a small number of patients. However, these variations did not significantly lead to iron overload.