Investigation of the mechanism of copy number variations involving the α-globin gene cluster on chromosome 16: two case reports and literature review

作者：Zhu, Dina; Xu, Linlin; Zhang, Yanxia; Liang, Guanxia; Wei, Xiaofeng; Li, Liyan; Jin, Wangjie; Shang, Xuan^*

来源：Molecular Genetics and Genomics, 2023, 298(1): 131-141.

DOI：10.1007/s00438-022-01968-1

• alpha-globin gene cluster
• Copy number variation
• Rearrangement
• Thalassemia

Thalassemia is one of the most common single-gene disorder worldwide. An important genetic cause of thalassemia is copy number variations (CNVs) in the alpha-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 (alpha alpha alpha alpha(159)) 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 beta(CD41-42) mutation and --(SEA )deletion separately, alpha alpha alpha alpha(159) and --(259) resulted in a patient with beta-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 alpha-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 alpha-globin gene cluster systematically.

• 单位
  南方医科大学