Wu Man-Yu, Li Jian, Li Shu-Chen, Li Ru, Liao Can, Li Dong-Zhi
Prenatal Diagnostic Center, Guangzhou Women & Children Medical Center affiliated to Guangzhou Medical University , Guangzhou, Guangdong , People's Republic of China.
Hemoglobin. 2015;39(4):256-9. doi: 10.3109/03630269.2015.1039026. Epub 2015 May 27.
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.
HKαα（香港αα）等位基因是α-珠蛋白基因簇的一种不寻常重排，包含-α(3.7)（向右）和ααα（反4.2）交叉缺失/插入。在我们的地中海贫血筛查项目中，我们鉴定出10名成年人和2名新生儿，他们被证实是HKαα和东南亚缺失型（--(SEA)）的复合杂合子。他们的血液学数据显示出典型的α地中海贫血（α-thal）特征。基于常规缺口聚合酶链反应（gap-PCR）的检测方法显示，α-珠蛋白基因簇中存在-α(3.7)、--(SEA)和正常的α2等位基因。这些令人困惑的结果表明，可能存在由α-珠蛋白基因簇之间重组等位基因的反复不等交换产生的更复杂的衍生等位基因。两轮巢式PCR策略证实了HKαα的诊断。考虑到中国地中海贫血高发地区的大规模人群筛查，当前的诊断策略可能需要相应修改。HKαα的检测将提高遗传咨询的准确性，特别是在一方是--(SEA)携带者而另一方通过常规缺口PCR方法鉴定为携带-α(3.7)缺失的夫妇中。
