Mild α-Thalassemia Caused by a Mosaic α-Globin Gene Mutation

Abstract

We describe a new α-globin chain variant in a Chinese subject. This novel variant, with a Val→Met substitution at codon 93 of the α-globin chain, has been named Hb Qingcheng (HBA1: c.280G>A) for where the proband was born. A woman with somatic mosaicism for Hb Qingcheng presented with the phenotype of mild α-thalassemia (α-thal).

Keywords:

• α-Globin chain variant
• α-thalassemia (α-thal)
• Hb Qingcheng

Disclosure statement

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

Figure 1. The level of mosaic HBA1 mutation in the patient. Using next-generation sequencing (NGS), we detected the HBA1: c.280G > A mutation (18.46%) (top), and it can also be detected by Sanger sequencing (bottom). To evaluate the low-level mosaicism of this variant, we used deep sequencing (>5000×) of the targeted allele by amplicon-based NGS. The region containing the Hb Qingcheng variant was amplified with designed primers targeting the HBA1 gene and long-range DNA polymerase (TaKaRa LA Taq Hot Start; TaKaRa Bio, Osaka, Japan). Amplicon was checked by gel electrophoresis, and was fragmented by sonication. Paired-end libraries were prepared following the Illumina protocol (Illumina, San Diego, CA, USA). Bar-coded samples were quantified by Qubit (Life Technologies, Eugene, OR, USA) and sequenced using the Illumina NexSeq 500 sequencing platform (Illumina).

Additional information

Funding

This study was supported by the Guangzhou Institute of Pediatrics/Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong Province, People’s Republic of China [IP-2019–004].