Characterization of a Novel 71.8 kb α0-Thalassemia Deletion and Subsequent Summary of a Practical Procedure for Thalassemia Molecular Diagnosis
Characterization of a Novel 71.8 kb α0-Thalassemia Deletion and Subsequent Summary of a Practical Procedure for Thalassemia Molecular Diagnosis
复制标题
DOI：
10.1080/03630269.2020.1790385
复制
发表时间：
2020-07
期刊：
影响因子：
1
通讯作者：
Mingli Xu;Jiachun Qin;Biyan Chen;Xuexi Yang;Haiping Liu;Wei-Xi Yuan;Jian-mei Zhong;Li-Min Huang-Li-Min-Huan
中科院分区：
文献类型：
--
作者：
Mingli Xu;Jiachun Qin;Biyan Chen;Xuexi Yang;Haiping Liu;Wei-Xi Yuan;Jian-mei Zhong;Li-Min Huang-Li-Min-Huan
地中海贫血是世界上最常见的单基因遗传性疾病。根据基因型-表型相关性原理，地中海贫血突变的鉴定是临床诊断和治疗的必要前提。因为只有常见的突变是常规检测，罕见或未确定的突变的鉴定是临床实验室的一个挑战。本研究采用多重连接依赖探针扩增（MLPA）、靶向-下一代测序（targeted-NGS）、缺口-聚合酶链反应（gap-PCR）和桑格测序技术，对1例经常规分子筛查后表现出表型-基因型相关性不一致的先证者进行了研究。最终，一个新的71.8 kb缺失（--71.8）被鉴定和表征，包括HBZ（α 2），HBA 2（α2）和HBA 1（α1）基因，并导致α0-地中海贫血（α0-塔尔贫血）。在此基础上，总结了一套实用的地中海贫血筛查方法，为地中海贫血的分子筛查和临床诊断，尤其是未确定突变或新突变的鉴定提供了指导。
Abstract Thalassemia is the most common monogenic disorder around the world. Based on the principle of genotype–phenotype correlation, identification of thalassemia mutations is the essential prerequisite for clinical diagnosis and management. Because only common mutations are routinely detected, the identification of rare or undetermined mutations is a challenge for clinical laboratories. Herein, a proband presenting with inconsistent phenotype–genotype correlation after routine molecular screening was investigated by multiplex ligation-dependent probe amplification (MLPA), targeted-next generation sequencing (targeted-NGS), gap-polymerase chain reaction (gap-PCR) and Sanger sequencing. Eventually, a novel 71.8 kb deletion (– −71.8) was identified and characterized, which included HBZ (ζ), HBA2 (α2), and HBA1 (α1) genes and was causing α0-thalassemia (α0-thal). Furthermore, we summarized a practical procedure based on accumulated experience in studies and clinical practice, which can be a guide for molecular screening and clinical diagnosis of thalassemia, especially for identification of undetermined or novel mutations.