Molecular characterization and clinical presentation of HKαα and anti‐HKαα alleles in southern Chinese subjects

Abstract

The HKαα allele is a rearrangement occurring in the α-globin gene cluster containing both the -α(3.7) and ααα(anti4.2) unequal crossover junctions. The anti-HKαα allele is the reciprocal product containing both the -α(4.2) and ααα(anti3.7) unequal crossover junctions, which had been predicted but had not been detected previously. The phenotypic feature and population frequency of these two unusual alleles were not described. We report the identification of nine individuals carrying the HKαα allele and two individuals carrying the anti-HKαα allele in southern China and describe their phenotype and haplotype data. The molecular structures of HKαα allele and anti-HKαα allele were confirmed by two-round nested polymerase chain reaction assay. The mechanism of origin of both alleles is related to probably simultaneous double crossover. Heterozygotes of HKαα or anti-HKαα allele show a normal hematological phenotype. Finally, we report the carrier rates of these both alleles in the Guangxi Zhuang Autonomous Region of southern China, namely, ∼0.07% for the HKαα allele and ∼0.02% for the anti-HKαα allele.

Compound Heterozygosity for HKααand anin CisDeletion of DoubleαGenes Presents asα-Thalassemia Trait

“…This supposition was confirmed by our findings. As with the --SEA allele, the adult individuals with the HKaa/--SEA genotype presented with a typical a-thal trait phenotype, similar to those previously reported (5,14). This will provide some clinical implications in the regions with different types of deletional a-thal (15).…”

“…In a recent study, the HKaa carrier rate was reported to be 0.07% in the Guangxi Zhuang Autonomous Region, a southern province of China (5). In daily practice, simple HKaa carriers could be mistaken for -a 3.7 allele carriers, as the individuals described in this study.…”

“…The frequency of this allele has recently been reported in a Chinese population (5). Since our routine gap-PCR assay for a-thal only targets --SEA , -a 3.7 and -a 4.2 deletions, but not triplicated a genes (e.g.…”

The Frequency of α-Globin Gene Triplication in a Southern Chinese Population

“…MLPA can also discriminate between heterozygote and homozygote triplication. For samples with either an aaa anti3.7 or aaa anti4.2 junction, the tworound nested PCR strategies were also used to detect the HKaa or anti-HKaa allele according to previous studies [8,9].…”

Neonatal screening for α‐thalassemia by cord hemoglobin Barts: how effective is it?

“…It consists of an intact a2-gene and an a1/a2 fusion gene (-a 3.7 ) with neither decreased nor enhanced agene dosage. In a recent study, the HKaa carrier rate was reported to be 0.07% in the Guangxi Zhuang Autonomous Region, a southern province of China (10). As our routine gap-PCR assay for a-thalassemia mainly targets on -SEA , -a 3.7 , and -a 4.2 deletions, but not triplicated a-genes (e.g., aaa anti4.2 and aaa anti3.7 ), simple HKaa carriers would be mistaken for -a 3.7 allele.…”