Mild Thalassemic Effect of Heterozygous Hb Sogn in a Large Cohort from Routine Hemoglobinopathy Investigation

Hemoglobin (Hb) Sogn is a rare Hb variant discovered in Norwegians and their descendants. Previous reports suggested no clinical symptoms in the heterozygote, but mild <i>in vitro</i> instability of the variant. Our recent clinical observations prompted suspicion of mild hematological abnormalities. This study aimed to evaluate hematological parameters and Hb fractions in individuals heterozygous for Hb Sogn, compared with those with Hb D-Punjab, to confirm or refute this suspicion. Data from 105 individuals with Hb Sogn and 145 with Hb D-Punjab were evaluated. Hematological parameters (Hb, RBC, MCH) and Hb fractions were compared using Mann-Whitney U tests. Different exclusion criteria were applied in the analysis for different parameters due to age- and sex-dependent reference intervals. <i>In silico</i> tools were used to predict pathogenicity. Individuals with Hb Sogn had lower MCH (median 28 pg vs 29 pg) and a lower variant fraction (median 33.6% vs 40.9%) compared with Hb D-Punjab. The HbA₂ fraction was higher in the Hb Sogn group (median 3.3% vs 2.9%). <i>In silico</i> prediction suggested a functional impact of Hb Sogn but did not reveal an effect on splicing. This study, involving the largest cohort of Hb Sogn carriers to date, suggests that heterozygous Hb Sogn exhibits a mild thalassemic phenotype. These findings may explain slightly reduced MCH values in affected individuals and could reduce the need for extended α-thalassemia investigation.