Abstract
Thalassemia is one of the most common single-gene disorder worldwide. An important genetic cause of thalassemia is copy number variations (CNVs) in the α-globin gene cluster. However, there is no unified summary and discussion on the detailed information and mechanisms of these CNVs. In this study, two novel CNVs, a tandem duplication (αααα159) and deletion (--259), were identified in two Chinese families with thalassemia patients, according to the results of hematologic analysis, routine genetic testing for thalassemia, multiplex ligation-dependent probe amplification (MLPA), next-generation sequencing (NGS) and other molecular methods. Co-inherited with βCD41–42 mutation and --SEA deletion separately, αααα159 and --259 resulted in a patient with β-thalassemia intermedia and a lethal fetus with Hb Bart’s hydrops fetalis syndrome, respectively. Next, a literature review was performed to summarize all known CNVs involving the α-globin gene cluster. The molecular structure characteristics of these CNVs were analyzed and the possible mechanism was explored. It is the first time to analyze the generation mechanism of genome arrangements in the α-globin gene cluster systematically.
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Acknowledgements
We thank the patient and his family for their reliance and cooperation.
Funding
This work was supported by research funding from the National Natural Science Foundation of China (Grant Number 81870148); National Key Research and Development Program of China (Grant Number 2017YFC1001800, 2017YFC1001804); Guangdong Basic and Applied Basic Research Foundation (Grant Number 2019A1515011545, 2022A1515011988); the Southern Medical University Innovation Training Program for Undergraduate Students (Grant Number 201912121027, S202012121059).
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DZ: Conceptualization, Investigation, Formal analysis, Writing—Original draft, Writing—Review & Editing. LX: Conceptualization, Investigation, Formal analysis. YZ: Methodology, Formal analysis. GL: Formal analysis. XW: Resources, Project administration. LL and WJ: Resources. XS: Conceptualization, Resources, Writing—Review & Editing, Funding acquisition.
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This study was approved by the Medical Ethics Committee of Nanfang Hospital, an affiliate of Southern Medical University, and conformed to the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Communicated by Shuhua Xu.
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Zhu, D., Xu, L., Zhang, Y. et al. Investigation of the mechanism of copy number variations involving the α-globin gene cluster on chromosome 16: two case reports and literature review. Mol Genet Genomics 298, 131–141 (2023). https://doi.org/10.1007/s00438-022-01968-1
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DOI: https://doi.org/10.1007/s00438-022-01968-1