Abstract
Copy number variations (CNVs) involving the α-globin gene cluster can lead to an imbalance in the proportion of α- and β-globin chains and consequently cause clinical symptoms of β-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with β thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous β0 mutation of Codon17 (A > T) and a full duplication of the α-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5′ untranslated region of β-Globin (HBB: c. −175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.
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Acknowledgements
The authors would like to thank Dr. Dongzhi Li and Dr. Fan Jiang from Guangzhou Women and Children Medical Center affiliated to Guangzhou Medical University for the MLPA validation; Dr. Lipei Liu from BGI-Tianjin Co.,Ltd for the analysis of low-pass whole genome sequencing results.
Authorship contribution statement
Xiaohong He: Resources, Writing-original draft, Funding acquisition. Peirun Tian: Formal analysis, Writing-original draft, Writing-Review & Editing. Shanshan Peng: Investigation. Lei Pan: Data Curation.Shiping Chen: Methodology. Lijuan Zhong: Visualization.Yutao Du: Supervision, Project administration.Rui Zhang: Conceptualization, Writing - Review & Editing, Funding acquisition.
Disclosure statement
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.