Molecular Basis and Hematologic Phenotype of Hemoglobin H Disease Combined with Two Rare β-Globin Mutations

Abstract

In area where α-thalassemia and β-thalassemia are prevalent, the coinheritance of hemoglobin H disease (Hb H disease) and β-thalassemia are not uncommon and could result in complex thalassemia intermedia syndromes. In this study, we investigate the hematological and molecular characteristics of two previously undescribed cases that co-inherited Hb H disease and rare β-globin gene (HBB) mutations found in Chinese populations. Proband I was a boy with Hb H disease in association with IVS-II-5(G > C) (HBB:c0.315 + 5G > C) mutation. Proband II was a boy with a combination of Hb H and Hb Zengcheng [β114(G16) Leu > Met; HBB:c.343C > A]. Both of them had mild hypochromic microcytic anemia, and neither had ever received a blood transfusion. In both cases, the level of Hb A₂ was within normal range, and no Hb H was detected, but a small amount of Hb Bart’s was observed in proband I. Routine DNA analysis detected the deletional Hb H disease in both cases. IVS-II-5(G > C) (HBB:c0.315 + 5G > C) and Hb Zengcheng (HBB:c.343C > A) mutations were found by DNA sequencing of β-globin gene. The co-inheritance of Hb H disease with rare β-thalassemia may result in an atypical pattern of Hb H disease, and further investigation of rare genotypes should be conducted to avoid missed diagnosis.

Keywords:

• Hb H disease
• IVS-II-5 (G > C)
• Hb Zengcheng
• β-globin gene
• coinheritance

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the Guangxi Project of Scientific Research Basic Capacity Improvement of Young and Middle-aged College Teachers [no. 2020KY03020] and the Open Project of NHC Key Laboratory of Thalassemia Medicine [no. GJWJWPD202202]