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
• β-globin variant
• hemoglobinopathies
• inclusion body thalassemia
• unstable hemoglobin (Hb)

Acknowledgements

The authors acknowledge Dr. Bjørn Dalhus, Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway, for his input on the substitution’s effect on protein structure.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.