Compound Heterozygosity for HKαα and an in Cis Deletion of Double α Genes Presents as α-Thalassemia Trait

Abstract

The HKαα (Hong Kongαα) 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/insertion. During our thalassemia screening program, we identified 10 adult individuals and two newborns who were confirmed to be compound heterozygotes for HKαα and the Southeast Asian deletion (– –^SEA). Their hematological data showed a typical α-thalassemia (α-thal) trait. The routine gap-polymerase chain reaction (gap-PCR) based assay revealed the presence of –α^3.7, – –^SEA and normal α2 alleles in the α-globin gene clusters. These confusing findings indicated the existence of more complex derivative alleles produced possibly by repeated unequal crossover of recombinant alleles between α-globin gene clusters. A two-round nested PCR strategy confirmed the diagnosis of HKαα. Considering the large-scale population screening in the thalassemia-prevalent regions in China, the current diagnostic strategy might need to be modified accordingly. The detection of HKαα would improve accuracy in genetic counseling, especially in couples where one partner was a – –^SEA carrier and the other carries a –α^3.7 deletion identified by routine gap-PCR methods.

• α-Globin gene rearrangement
• α-thalassemia (α-thal)
• HKαα (Hong Kongαα)
• allele
• Southeast Asian deletion

Declaration of interest

This study was supported by grants from Natural Science (81100435) and Guangzhou Health Bureau (20121A021012), Guangzhou, Guangdong, People’s Republic of China. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.