Hb Calgary (HBB: c.194G>T): A Highly Unstable Hemoglobin Variant with a β-Thalassemia Major Phenotype

Abstract

We describe two unrelated patients, both heterozygous for an unstable hemoglobin (Hb) variant named Hb Calgary (HBB: c.194G>T) that causes severe hemolytic anemia and dyserythorpoietic, resulting in transfusion dependence and iron overload. The molecular pathogenesis is a missense variation on the β-globin gene, presumed to lead to an unstable Hb. The phenotype of Hb Calgary is particularly severe presenting as transfusion-dependent anemia in early infancy, precluding phenotypic diagnosis and highlighting the importance of early genetic testing in order to make an accurate diagnosis.

Keywords: Autosomal dominant thalassemia; hemoglobinopathies; inclusion body thalassemia; unstable hemoglobin (Hb); β-globin variant.