The HKαα (HongKongαα) allele is an unusual rearrangement of the α-globin gene cluster containing both the -α(3.7) (rightward) and ααα(anti 4.2) crossover deletion/duplication. The anti-HKαα (anti-HongKongαα) allele is the reciprocal product containing both the -α(4.2) (leftward) and ααα(anti 3.7) unequal crossover deletion/duplication. In clinical practice of thalassemia screening, gap-polymerase chain reaction (gap-PCR) approaches are used to detect the common -α(3.7) and -α(4.2) deletions of α-thalassemia (α-thal). Because the HKαα and anti-HKαα alleles also contain the single α-globin gene deletion, individuals with these alleles would be misdiagnosed as -α(3.7) or -α(4.2) carriers. This would likely produce misleading or incorrect information in genetic counseling. In this study, we investigated the HKαα and anti-HKαα alleles in Chinese carriers of silent deletional α-thal, and reported their frequencies to be 2.27 and 0.35% in -α(3.7) and -α(4.2) carriers, respectively. Given the rarity of the HKαα and anti-HKαα alleles, a routine screening for these two rearrangements are unlikely to be necessary on most occasions.
Thalassemia intermedia is an inherited hemoglobin disorder characterized by a significant genetic and clinical heterogeneity. A wide spectrum of different genotypes-homozygous, heterozygous, and compound heterozygous-have been found to be responsible for it. The authors describe a Chinese child of β-thalassemia heterozygote with the mutation IVS2-654 (C→T) (HBB:c.316-197C→T) presenting with severe thalassemia intermedia. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analyses of the α gene cluster revealed an approximate 146-kb duplication at 16p13.3 including the complete α gene cluster. The duplicated allele and the normal allele in trans result in a total of 6 active α genes. The severe clinical phenotype seemed to be related to the considerable excess of the α-globin and the β-globin deficit caused by the presence of the β-thalassemia. The α gene duplication should be considered in patients heterozygous for β-thalassemia who show a more severe phenotype than β-thalassemia trait.
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