A Novel 165 Kb Duplication Involving the α-Globin Gene Cluster Is Identified by Low-Pass Whole Genome Sequencing in a Chinese Thalassemia Intermedia Patient.

IF 1.2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiaohong He, Peirun Tian, Lijuan Zhong, Shanshan Peng, Shiping Chen, Lei Pan, Yutao Du, Rui Zhang
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引用次数: 0

Abstract

Copy number variations (CNVs) involving the α-globin gene cluster can lead to an imbalance in the proportion of α- and β-globin chains and consequently cause clinical symptoms of β-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with β thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous β0 mutation of Codon17 (A > T) and a full duplication of the α-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5' untranslated region of β-Globin (HBB: c. -175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.

通过低通滤波全基因组测序在一名中国地中海贫血症患者体内发现涉及α-球蛋白基因簇的 165 Kb 重复。
涉及α-球蛋白基因簇的拷贝数变异(CNV)可导致α-和β-球蛋白链比例失调,从而引起β地中海贫血的临床症状。在我们的病例中,一名 6 岁男孩被临床诊断为中型 β 地中海贫血症,他和家人一起入院接受进一步的基因诊断。我们采用了靶向测序和第三代测序(TGS)来检测地中海贫血基因的可能变异。结果显示,该患者的第 17 号密码子(A > T)发生了杂合性 β0 突变,α-球蛋白基因簇发生了全重复,这两个基因分别遗传自他的母亲和父亲。此外,仅在该患者体内检测到了β-球蛋白(HBB:c. -175 (G > A))5'非翻译区内的一个新的点突变。这项研究表明,lpWGS 似乎是检测与地中海贫血症有关的大型 CNVs 的一种强有力的替代方法,其第二目的是获得更多的断点信息,并同时在基因组范围内检测其他致病性 CNVs。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Hemoglobin
Hemoglobin 医学-生化与分子生物学
CiteScore
1.70
自引率
10.00%
发文量
59
审稿时长
3 months
期刊介绍: Hemoglobin is a journal in the English language for the communication of research and information concerning hemoglobin in humans and other species. Hemoglobin publishes articles, reviews, points of view The journal covers topics such as: structure, function, genetics and evolution of hemoglobins biochemical and biophysical properties of hemoglobin molecules characterization of hemoglobin disorders (variants and thalassemias), consequences and treatment of hemoglobin disorders epidemiology and prevention of hemoglobin disorders (neo-natal and adult screening) modulating factors methodology used for diagnosis of hemoglobin disorders
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