Genetic profiles and hematological characteristics of the α-Hb variant Hb Chumphae (HBA2:c.32T>A) in association with –SEA deletion α0-thalassemia

OBJECTIVE: Hemoglobin (Hb) variants and thalassemia interactions create complex syndromes, complicating diagnosis. This study aimed to characterize the molecular basis, genetic profile, and potential hematological features of a rare α-hemoglobin variant. METHODS: A 44-year-old Thai male presented with unspecified chronic anemia with hepatosplenomegaly. Hematological data were obtained using a standard automated cell counter. Hemoglobin analysis was performed using high-performance liquid chromatography and capillary electrophoresis. Mutational and globin haplotypes were analyzed using polymerase chain reaction and sequencing. The pathogenicity of the mutant gene was predicted, and novel diagnostic methods based on allele-specific polymerase chain reaction were developed. RESULTS: -thalassemia (SEA deletion) was identified. Predictions and classifications of pathogenicity indicated a pathogenic effect. Polymerase chain reaction-restriction fragment length polymorphisms and allele-specific polymerase chain reaction assays successfully identified this mutation. An α-haplotypic [- - M - - - -] was possibly associated with Hb Chumphae. CONCLUSIONS: -thalassemia as a compound heterozygote leads to severe anemia worse than hemoglobin H disease. The diagnosis of Hb Chumphae is challenging as high-performance liquid chromatography and capillary electrophoresis chromatograms mimic those of Hb Bart's. Accurate diagnosis requires globin genotyping.