First Report of Co‐Inheritance of Hemoglobin British Columbia (
HBB
:c.
304G
>A) and β‐Thalassemia
IVS
Kimia Fathalizade, Mahsa Kiani Bigdeli, Seyed Sajad Eghbali, Mohammadtaghi Ghiyasi, Roz Rastgoo, Mohammad Javad Mousavi ABSTRACT
Background
Hemoglobin British Columbia is a rare high‐oxygen‐affinity β‐globin variant caused by the HBB:c.304G>A substitution. Its detection is exceptionally uncommon, particularly in the Middle East, and may lead to diagnostic pitfalls when relying solely on hemoglobin separation techniques. Precise molecular characterization is therefore essential for accurate differentiation from other hemoglobinopathies and for expanding knowledge of their regional distribution.
Case Presentation
We report a 25‐year‐old asymptomatic Iranian male who was incidentally identified during routine premarital screening due to the presence of an unexpected hemoglobin band. Comprehensive evaluation was performed using capillary zone electrophoresis (CZE), targeted analysis of common α‐globin deletions, full sequencing of the α‐ and β‐globin genes, and long‐range PCR for α‐gene triplications.
Results
CZE revealed a major abnormal hemoglobin fraction (73.2%), with HbA at 21.7% and HbA 2 at 5.1%. α‐Globin gene analysis showed no mutations. β‐Globin gene sequencing demonstrated compound heterozygosity for Hb British Columbia (HBB:c.304G>A) and the β‐thalassemia variant IVS‐I‐6 (HBB:c.92+6T>C), a combination not previously reported. Despite the presence of two β‐globin variants, the patient exhibited normal hematologic and biochemical parameters and no clinical symptoms.
Conclusion
This is the first documented case of co‐inheritance of Hb British Columbia and the IVS‐I‐6 β‐thalassemia mutation in Iran. The case underscores the crucial role of molecular diagnostics in resolving atypical electrophoretic patterns, preventing misclassification of rare hemoglobin variants, and enriching the understanding of the hemoglobinopathy spectrum in diverse populations.