Hb H Disease Results from Compound Heterozygosity of – –^SEA and –α^MAL3.5 in a Chinese Family

Abstract

The α⁺-thal deletion of 3.557 kb (NG_000006.1: g.32745_36301del, –α^MAL3.5), involving the entire α2-globin gene, was identified in a Chinese family by multiplex ligation-dependent probe amplification (MLPA) followed by gap-polymerase chain reaction (gap-PCR) and sequencing. The proband, a compound heterozygote for this mutant gene and the Southeast Asian (– –^SEA; NG_000006.1: g.26264_45564del19301) deletion, had a phenotype of Hb H disease [hemoglobin (Hb) 7.6 g/dL, mean corpuscular volume (MCV) 60.0 fL, Hb H (β4) 0.7%, Hb Bart’s (γ4) 2.4% and Hb A₂ 1.1%]; one of her sisters with same genotype showed a similar phenotype. Another two family members, who were carriers of this mutant gene, had a hematological phenotype of a silent α-thal. The 5' and 3' breakpoints of this deletion are located at the Y2 and Y1 boxes, respectively, therefore, it probably originated from an unequal crossover between these two homologous boxes. This mutation constitutes an additional heterogeneous defect causing α-thal in the Chinese population and would be valuable for elucidating the arrangement in the human α-globin gene cluster.

Keywords:

• α-Globin gene cluster
• –α^MAL3.5
• α-thalassemia (α-thal)
• Hb H disease

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was funded by the Dongguan Social Development Project [#201750715007181].