A Novel Human β-Globin Gene Variant [Hb London-Ontario, HBB: c.332T>G] is Associated with Transfusion-Dependent Anemia in a Patient with a Hemoglobin Electrophoresis Pattern Consistent with β-Thalassemia Trait.

We present the case of a novel β-globin gene variant associated with early-onset transfusion-dependent anemia compatible with a β-thalassemia major (β-TM) phenotype in a patient of British descent. As a child, our patient developed chronic symptomatic anemia with hemoglobin (Hb) nadirs of 3.0 g/dL. She started receiving occasional transfusions by the age of 13 years and became transfusion-dependent by the age of 32 years. Work-up performed at our center showed a Hb electrophoresis compatible with β-thalassemia (β-thal) trait. Polymerase chain reaction (PCR) of the β-globin gene detected a novel mutation situated at codon 110 (CTG). This missense mutation led to a substitution of the thymine nucleotide (nt) base for guanine (CGG) at position 332 (HBB: c.332T>G). We have named this new mutation Hb London-Ontario. The majority of previously described dominant allelic mutations of the β-globin gene led to a β-thal intermedia (β-TI) phenotype. The heterozygous mutation which was detected in our patients is unique at it leads to a more severe β-TM phenotype. We suspect this is a de novo mutation of which the mother of our patient, who was reported to have a form of thalassemia, was the proband.