A Novel Human beta-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 beta-Thalassemia Trait

摘要

We present the case of a novel p-globin gene variant associated with early-onset transfusion-dependent anemia compatible with a p-thalassemia major (P-TM) phenotype in a patient of British descent. As a child, our patient developed chronic symptomatic anemia with hemoglobin (Hb) nadirs of 3.0g/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 p-thalassemia (p-thal) trait. Polymerase chain reaction (PCR) of the p-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 p-globin gene led to a P-thal intermedia (p-TI) phenotype. The heterozygous mutation which was detected in our patients is unique at it leads to a more severe p-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 thalas-semia, was the proband.