Shao Mingkun, Wan Yaoyao, Cao Weipeng, Yang Juan, Cui Di, Ma Minhui, Hu Wanqin
Department of OB and GYN, The Second Affiliated Hospital of Kunming Medical University, Yunnan, China.
Department of Cardiovascular Medicine, The Second People's Hospital of Honghe Autonomous Prefecture, Yunnan, China.
Front Med (Lausanne). 2023 Jul 13;10:1192279. doi: 10.3389/fmed.2023.1192279. eCollection 2023.
Thalassemia is a common inherited hemoglobin disorder caused by a deficiency of one or more globin subunits. Substitution variants and deletions in the gene are the major causes of β-thalassemia, of which large fragment deletions are rare and difficult to be detected by conventional polymerase chain reaction (PCR)-based methods.
In this study, we reported a 26-year-old Han Chinese man, whose routine blood parameters were found to be abnormal. Hemoglobin testing was performed on the proband and his family members, of whom only the proband's mother had normal parameters. The comprehensive analysis of thalassemia alleles (CATSA, a long-read sequencing-based approach) was performed to identify the causative variants. We finally found a novel 10.8-kb deletion including the β-globin () gene (Chr11:5216601-5227407, GRch38/hg38) of the proband and his father and brother, which were consistent with their hemoglobin testing results. The copy number and exact breakpoints of the deletion were confirmed by multiplex ligation-dependent probe amplification (MLPA) and gap-polymerase chain reaction (Gap-PCR) as well as Sanger sequencing, respectively.
With this novel large deletion found in the gene in China, we expand the genotype spectrum of β-thalassemia and show the advantages of long-read sequencing (LRS) for comprehensive and precise detection of thalassemia variants.
地中海贫血是一种常见的遗传性血红蛋白疾病，由一种或多种珠蛋白亚基缺乏引起。β-地中海贫血的主要病因是基因中的替换变异和缺失，其中大片段缺失罕见，难以通过传统的基于聚合酶链反应（PCR）的方法检测到。
在本研究中，我们报告了一名26岁的汉族男性，其常规血液参数异常。对先证者及其家庭成员进行了血红蛋白检测，其中只有先证者的母亲参数正常。采用地中海贫血等位基因综合分析（CATSA，一种基于长读长测序的方法）来鉴定致病变异。我们最终发现先证者及其父亲和兄弟存在一个新的10.8kb缺失，包括β-珠蛋白（）基因（Chr11:5216601-5227407，GRch38/hg38），这与他们的血红蛋白检测结果一致。分别通过多重连接依赖探针扩增（MLPA）、缺口聚合酶链反应（Gap-PCR）以及桑格测序确认了缺失的拷贝数和确切断点。
在中国发现的这个新的β-珠蛋白基因大片段缺失，我们扩展了β-地中海贫血的基因型谱，并展示了长读长测序（LRS）在全面、精确检测地中海贫血变异方面的优势。
