Frequencies and hematological manifestations of the HKαα allele in southern Chinese population

Introduction: The HKαα (Hong Kong αα) allele containing both the -α^3.7 and ααα^anti4.2 is an unusual rearrangement of the α globin gene cluster. Currently, ααα^anti4.2 fragments cannot be detected through the routine thalassemia diagnostic kit. The genotype of -α^3.7/αα, HKαα/-α^3.7 and HKαα/αα is entirely the result of -α^3.7/αα by the gap-polymerase chain reaction (gap-PCR), which would cause some cases of the HKαα allele to be mistaken as -α^3.7/αα.

Methods: Genetic diagnosis was performed in 17166 cases, using single PCR and two-round nested PCR to detect the HKαα allele in 895 cases. It showed -α^3.7 and α2 bands by gap-PCR, and reverse dot-blot assays were performed to detect the non-deletional α thalassemia point mutations and β thalassemia point mutations.

Results: The HKαα allele was found in 56 samples. The rates of HKαα/αα, HKαα/-α^3.7 and HKαα/--^SEA were 4.92%, 0.67% and 0.67%. The rate of the HKαα allele was 0.33% in a southern Chinese population. In the HKαα/αα thalassemia group, the levels of hemoglobin (Hb), mean cell volume (MCV), and mean cell hemoglobin (MCH) were similar to the -α^3.7/αα thalassemia group. The hematology of the HKαα/--^SEA carriers was similar with the α⁰ thalassemia carriers, and Hb is usually over 100 g/l. The two families carrying HKαα/--^SEA genotype chose to retain the fetuses in our study.

Conclusions: There was a certain proportion of the HKαα allele in southern Chinese population, and the hematologic manifestations were mild. Differential diagnosis of HKαα genotype from -α^3.7/αα can provide more accurate genetic diagnosis and clinical thalassemia genetic counseling.