Xu Jianfei, Hu Liang, Wen Lijuan, Cao Xianzhen, Xu Hongyan, Luo Qi, Long Yuhong, Ji Tingyu, Sun Lifang, Wei Fengxiang
Jiamusi University, Jiamusi, China.
Longgang District Maternity & Child Healthcare Hospital of Shenzhen City (Affiliated Shenzhen Women and Children's Hospital (Longgang) of Shantou University Medical College), Shenzhen, China.
Front Genet. 2025 Mar 10;16:1518392. doi: 10.3389/fgene.2025.1518392. eCollection 2025.
To describe the characterization of a novel deletion causing α-thalassemia.
The proband was a 4-year-old boy who presented with abnormal hematological parameters identified during routine blood investigation conducted for a cold. Three common α-globin gene deletions, three mutations, and 17 mutations in the β-globin gene were detected using PCR-flow fluorescence hybridization. Next-generation sequencing (NGS) and CNVplex technologies were employed to identify potential rare pathogenic mutation types. The CNVplex technology leverages variations in the lengths of linkage sequences of differential sequences at the same locus to produce linkage products of varying lengths, thereby enabling the detection of multiple loci within the same system. The newly identified deletions were further validated using customized third-generation sequencing (TGS) and Sanger sequencing.
In this study, hematological analysis indicated a potential diagnosis of thalassemia in the proband, characterized by typical microcytic hypodermic features. A novel 134-kb deletion in the α-globin gene cluster was identified in this proband using the CNVplex technology. This deletion encompasses the genes , , , , and . Furthermore, we confirmed the gene deletion through customized TGS testing and Sanger sequencing, allowing us to determine the size of the deletion. The results suggest that this represents a new deletion of 146 kb that has not been previously reported, and we hypothesize that this deletion is likely the primary cause of the α-thalassemia trait observed in the proband.
描述一种导致α地中海贫血的新型缺失的特征。
先证者是一名4岁男孩，因感冒进行常规血液检查时发现血液学参数异常。采用聚合酶链反应-流动荧光杂交技术检测了三种常见的α珠蛋白基因缺失、三种突变以及β珠蛋白基因中的17种突变。采用下一代测序（NGS）和CNVplex技术来识别潜在的罕见致病突变类型。CNVplex技术利用同一基因座上差异序列连锁序列长度的变化产生不同长度的连锁产物，从而能够在同一系统中检测多个基因座。使用定制的第三代测序（TGS）和桑格测序对新发现的缺失进行进一步验证。
在本研究中，血液学分析表明先证者可能诊断为地中海贫血，其特征为典型的小细胞低色素性表现。利用CNVplex技术在该先证者中鉴定出α珠蛋白基因簇中一个新的134kb缺失。该缺失包含基因 、 、 、 和 。此外，我们通过定制的TGS检测和桑格测序确认了基因缺失，从而确定了缺失的大小。结果表明，这代表了一个此前未报道过的146kb的新缺失，我们推测该缺失可能是先证者中观察到的α地中海贫血特征的主要原因。
