4.5 Article

Characterization of two novel Alu element-mediated α-globin gene cluster deletions causing α0-thalassemia by targeted next-generation sequencing

期刊

MOLECULAR GENETICS AND GENOMICS
卷 295, 期 2, 页码 505-514

出版社

SPRINGER HEIDELBERG
DOI: 10.1007/s00438-019-01637-w

关键词

alpha-thalassemia; Multi-species conserved sequence; Targeted next-generation sequencing; Breakpoints; Copy number variations; Rearrangement mechanisms

资金

  1. National Key R&D Program of China [2018YFA0507800, 2018YFA0507803]
  2. Natural Science Foundation of China [81870148]
  3. Natural Science Foundation of Guangdong Province [2017A030313673]
  4. Guangxi health and family planning commission [Z20170528]

向作者/读者索取更多资源

alpha-thalassemia is an inherited blood disorder commonly caused by deletions or point mutations involving one or both alpha-globin genes. Recent studies shed new light on the critical role of upstream enhancers multi-species conserved sequences (MCSs) in the ordered regulation of alpha-globin gene expression. Herein, we reported two unrelated probands with deletions in alpha-globin genes and MCSs, respectively. The proband from Family A is a compound heterozygote carrying a known alpha(+) mutation (-alpha(3.7)) and a novel 60.2 kb deletion causing the absence of both alpha-globin genes. The proband from Family B, on the other hand, is a compound heterozygote with a known alpha(0) mutation (--(SEA)) and a novel deletion involving only upstream regulatory elements MCS-R1, R2 and R3, while the alpha-globin genes remain intact. Notably, both these two patients suffered varied extent of anemia, indicating that the loss of enhancer elements could equally lead to reduced synthesis of alpha-globin. Upon these observations, we then confirmed the exact breakpoints of these two novel deletions using a targeted next-generation sequencing (NGS) previously established by our group, which may enable further elucidation of the rearrangement mechanisms on these deletions and functional dissection of MCSs. Taken together, our study reports a reliable NGS-based molecular screening approach for accurate identification of copy number variations (CNVs) in the alpha-globin cluster and the genetic diagnosis of these two probands may help to extend the spectrum of alpha-thalassemia mutations in Chinese population.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据