Molecular Characterization of Complex Thalassemia with Multiple Variants in β-Globin Gene Cluster and the Identification of a Novel Structural Rearrangement in γ-Globin Gene.

IF 1.2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yonghua Xu, Haiyan Luo, Ting Huang, Yuan Fang, Pengpeng Ma, Yan Yang, Junhui Shao, Yongyi Zou, Yanqiu Liu, Jihui Zhou, Bicheng Yang
{"title":"Molecular Characterization of Complex Thalassemia with Multiple Variants in β-Globin Gene Cluster and the Identification of a Novel Structural Rearrangement in γ-Globin Gene.","authors":"Yonghua Xu, Haiyan Luo, Ting Huang, Yuan Fang, Pengpeng Ma, Yan Yang, Junhui Shao, Yongyi Zou, Yanqiu Liu, Jihui Zhou, Bicheng Yang","doi":"10.1080/03630269.2025.2484236","DOIUrl":null,"url":null,"abstract":"<p><p>Molecular characterization was performed for investigation of β-globin gene cluster in a pregnant Chinese female with mild microcytic hypochromic anemia accompanied with complicated hemoglobin fractions. Routine hematological parameters and hemoglobin analyses were conducted using an automated cell counter and capillary electrophoresis, separately. Long-read single molecule real time (SMRT) sequencing was employed to molecularly characterize this individual. Hematological indices showed mild microcytic hypochromic anemia, and hemoglobin analyses demonstrated normal HbA2 percentage of 2.3% and increased HbF value of 13.1% in this female. SMRT thalassemia genetic testing showed a heterozygous β<sup>+</sup> mutation <i>HBB</i>:c0.316-197C > T (β<sup>IVS-II-654 (C>T)</sup>) and heterozygous <i>HBG2:</i>c.-211C > T (-158Gγ (C > T)), which has independently been reported to result in elevated HbF levels. A variant <i>HBD</i>: c.-127T > C (-77 (T > C)) was also identified in the promoter region, which has been frequently reported to result in normal HbA2 levels in patients with β-thalassemia. All the three variants were further validated by Sanger sequencing. Moreover, SMRT analysis unraveled a novel duplicated structural variation of <i>HBG1</i>/<i>HBG2</i> (<sup>G</sup>γ<sup>A</sup>γ/<sup>-158(C>T)GγGγGγAγ</sup>), a rearrangement of four γ-globin genes including one entire <i>HBG1</i> and three entire <i>HBG2</i> in one chromosome. We herein first described a novel structural quadruplet γ-globin genes of <i>HBG2</i> by SMRT and reported the molecular characterization of a complex thalassemia with variants involving <i>HBG1</i>/<i>HBG2</i>, <i>HBD</i> and <i>HBB</i> genes. Our work may facilitate genetic counseling and bring insight into future diagnosis of complex thalassemia.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-4"},"PeriodicalIF":1.2000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hemoglobin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03630269.2025.2484236","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Molecular characterization was performed for investigation of β-globin gene cluster in a pregnant Chinese female with mild microcytic hypochromic anemia accompanied with complicated hemoglobin fractions. Routine hematological parameters and hemoglobin analyses were conducted using an automated cell counter and capillary electrophoresis, separately. Long-read single molecule real time (SMRT) sequencing was employed to molecularly characterize this individual. Hematological indices showed mild microcytic hypochromic anemia, and hemoglobin analyses demonstrated normal HbA2 percentage of 2.3% and increased HbF value of 13.1% in this female. SMRT thalassemia genetic testing showed a heterozygous β+ mutation HBB:c0.316-197C > T (βIVS-II-654 (C>T)) and heterozygous HBG2:c.-211C > T (-158Gγ (C > T)), which has independently been reported to result in elevated HbF levels. A variant HBD: c.-127T > C (-77 (T > C)) was also identified in the promoter region, which has been frequently reported to result in normal HbA2 levels in patients with β-thalassemia. All the three variants were further validated by Sanger sequencing. Moreover, SMRT analysis unraveled a novel duplicated structural variation of HBG1/HBG2 (GγAγ/-158(C>T)GγGγGγAγ), a rearrangement of four γ-globin genes including one entire HBG1 and three entire HBG2 in one chromosome. We herein first described a novel structural quadruplet γ-globin genes of HBG2 by SMRT and reported the molecular characterization of a complex thalassemia with variants involving HBG1/HBG2, HBD and HBB genes. Our work may facilitate genetic counseling and bring insight into future diagnosis of complex thalassemia.

β-珠蛋白基因簇多变异复杂地中海贫血的分子特征及γ-珠蛋白基因新结构重排的鉴定
对1例伴有复杂血红蛋白组分的轻度小细胞性低色素贫血的中国孕妇进行了β-珠蛋白基因簇的分子鉴定。常规血液学参数和血红蛋白分析分别使用自动细胞计数器和毛细管电泳进行。采用长读单分子实时(SMRT)测序对该个体进行分子表征。血液学指标显示轻度小细胞性低色度贫血,血红蛋白分析显示HbA2正常2.3%,HbF升高13.1%。SMRT地中海贫血基因检测显示,杂合β+突变HBB:c0.316-197C >T (β ivs - ii -654 (C>T)))和杂合HBG2: C。-211C > T (-158Gγ (C > T))),有独立报道导致HbF水平升高。在启动子区域也发现了一种变体HBD: C - 127t > C (-77 (T > C)),这经常被报道导致β-地中海贫血患者的HbA2水平正常。所有三种变异均通过Sanger测序进一步验证。此外,SMRT分析揭示了HBG1/HBG2 (g - γ γ/-158(C>T) g - γ g - γ g - γ γ)的一个新的重复结构变异,这是一条染色体上四个γ-球蛋白基因的重排,包括一个完整的HBG1和三个完整的HBG2。本研究首先通过SMRT描述了HBG2中一种新的四联体结构γ-珠蛋白基因,并报道了一种涉及HBG1/HBG2、HBD和HBB基因变异的复杂地中海贫血的分子特征。我们的工作可能会促进遗传咨询,并为未来复杂地中海贫血的诊断带来洞察力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
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
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信