Two Novel α-Thalassemia Mutations CD 39 -C [Thr > Pro] and CD 109 ACC > CCC [Thr > Pro] Identified in Two Chinese Families: A Case Report

Abstract

We reported the identification of two rare α-thalassemia silent carriers with novel HBA1 mutations of CD 39 -C [Thr > Pro] (HBA1: c.114del; p.Thr39Profs*11) and CD 109 ACC > CCC [Thr > Pro] (HBA1: c.325A > C; p. Thr109Pro), respectively. The two probands were pregnant women diagnosed with mild hypochromic anemia or microcytic hypochromic anemia by routine blood tests. They started iron therapy before taking differential diagnosis from iron deficiency anemia. After wait and watch approach, they both accepted thalassemia genetic screening, which identified CD 39 -C [Thr > Pro] and CD 109 ACC > CCC [Thr > Pro], respectively. Due to inappropriate iron therapy, worse anemia and iron overload were noticed in the first proband, but no obvious side effect was found in both probands. Functional analysis showed that, relative to the wild type, CD 39 -C [Thr > Pro] considerably reduced the expression of the HBA1 protein while CD 109 ACC > CCC [Thr > Pro] only had a minor impact. Our study highlighted the importance of gestational thalassemia screening based on next-generation sequencing for identifying novel rare thalassemia variants and increased our understanding about the relationship between genotype and phenotype of α-thalassemia.

Keywords:

• Thalassemia
• iron deficiency anemia
• pregnancy
• next-generation sequencing
• HBA1

Acknowledgements

We thank the two families for participating in the study.

Author contributions

WZ conceived the study and wrote the manuscript. RZ and CW prepared the genetic data of two families. XD prepared and analyzed functional experiments. JD and ML analyzed patients and prepared the clinical data. All authors reviewed and approved the manuscript.

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 supported by the Program of Hubei Provinical Clinical Research Center for Precision Diagnosis of Complex Fetal Malformations (No. 2021LC002).