Hemoglobin Hekinan II (HBA1:c.84G>T): an electrophoretically silent α-globin variant missed by routine screening in...

This study aimed to characterize the molecular and hematologic features of hemoglobin (Hb) Hekinan II in northern Thailand and to evaluate its phenotypic expression when co-inherited with other hemoglobinopathies.

In total, 2314 blood samples were drawn for routine Hb analysis using high-performance liquid chromatography and capillary electrophoresis, and common α0-thalassemia deletions were detected by multiplex real-time polymerase chain reaction with high-resolution melting analysis. Targeted next-generation sequencing using DNA nanoball sequencing technology was applied to identify variations in the HBA1, HBA2, and HBB genes.

Routine laboratory screening failed to detect Hb Hekinan II in all cases. Molecular analysis identified 13 (0.6%) carriers. Individuals with heterozygous Hb Hekinan II showed normal Hb profiles and near-normal red blood cell indices, confirming its clinically silent nature. Co-inheritance with HbE resulted in mild microcytosis resembling the HbE trait, while more complex genotypes involving β0-thalassemia, α+-thalassemia, or additional α-globin variants produced variable hematologic phenotypes. All cases were detected only by molecular methods and were missed by conventional Hb typing.

Hemoglobin Hekinan II is a clinically benign but diagnostically challenging α-globin variant that cannot be reliably identified by routine screening. Integrating targeted molecular diagnostics is essential for accurate detection and genetic counseling.