Alpha-Thalassemia Caused by ααIVSI-1(AGGT> AGAT) (HBA1: c.95 + 1G > A) Mutation and its Combinations with Other Forms of Thalassemia or Hemoglobinopathy in Northern Thailand.

IF 0.7 4区 医学 Q4 HEMATOLOGY
Sakorn Pornprasert, Chedtapak Ruengdit, Manoo Punyamung, Orapan Sripichai
{"title":"Alpha-Thalassemia Caused by αα<sup>IVSI-1(AGGT> AGAT)</sup> (HBA1: c.95 + 1G > A) Mutation and its Combinations with Other Forms of Thalassemia or Hemoglobinopathy in Northern Thailand.","authors":"Sakorn Pornprasert, Chedtapak Ruengdit, Manoo Punyamung, Orapan Sripichai","doi":"10.1007/s12288-024-01895-8","DOIUrl":null,"url":null,"abstract":"<p><p>The αα<sup>IVSI-1(AGGT> AGAT)</sup> mutation is typically disregarded during routine thalassemia testing because of its mild or absent pathology in heterozygous individuals as well as its interactions with modulators that can result in variable phenotypes, particularly in β-thalassemia (β-thal) and hemoglobin E (HbE) carriers. This study was performed to analyze the αα<sup>IVSI-1(AGGT> AGAT)</sup> mutation in Northern Thailand using targeted next-generation sequencing (NGS). Hb analysis was performed by HPLC and/or CE methods. The α-thal-1 --<sup>SEA</sup>, --<sup>Thai</sup>, and --<sup>Chiang Rai</sup> type deletions were detected by real-time PCR with high-resolution melting analysis, and the α-thal-2 (-α<sup>3.7</sup> and -α<sup>4.2</sup>) deletion was detected by conventional gap-PCR. Thalassemia genotypes were further investigated using an NGS panel targeting the coding regions of the <i>HBA1</i>, <i>HBA2</i>, and <i>HBB</i> genes. The αα<sup>IVSI-1(AGGT> AGAT)</sup> mutation was misdiagnosed by routine thalassemia diagnostic methods. NGS results showed that 7 (3 Burmese and 4 Thai originations) of 1107 (0.63%) blood samples were heterozygous for the αα<sup>IVSI-1(AGGT> AGAT)</sup> mutation, which appeared in 5 different genotypes. Clinical and hematological features varied with their combination forms. The targeted NGS analysis utilized in this study is a promising genetic testing method for the identification of uncommon globin gene mutations. It shows particular promise in thalassemia screening and genetic counseling.</p>","PeriodicalId":49188,"journal":{"name":"Indian Journal of Hematology and Blood Transfusion","volume":"41 3","pages":"674-679"},"PeriodicalIF":0.7000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267114/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Indian Journal of Hematology and Blood Transfusion","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12288-024-01895-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/4 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The ααIVSI-1(AGGT> AGAT) mutation is typically disregarded during routine thalassemia testing because of its mild or absent pathology in heterozygous individuals as well as its interactions with modulators that can result in variable phenotypes, particularly in β-thalassemia (β-thal) and hemoglobin E (HbE) carriers. This study was performed to analyze the ααIVSI-1(AGGT> AGAT) mutation in Northern Thailand using targeted next-generation sequencing (NGS). Hb analysis was performed by HPLC and/or CE methods. The α-thal-1 --SEA, --Thai, and --Chiang Rai type deletions were detected by real-time PCR with high-resolution melting analysis, and the α-thal-2 (-α3.7 and -α4.2) deletion was detected by conventional gap-PCR. Thalassemia genotypes were further investigated using an NGS panel targeting the coding regions of the HBA1, HBA2, and HBB genes. The ααIVSI-1(AGGT> AGAT) mutation was misdiagnosed by routine thalassemia diagnostic methods. NGS results showed that 7 (3 Burmese and 4 Thai originations) of 1107 (0.63%) blood samples were heterozygous for the ααIVSI-1(AGGT> AGAT) mutation, which appeared in 5 different genotypes. Clinical and hematological features varied with their combination forms. The targeted NGS analysis utilized in this study is a promising genetic testing method for the identification of uncommon globin gene mutations. It shows particular promise in thalassemia screening and genetic counseling.

泰国北部ααIVSI-1(AGGT> AGAT) (HBA1: c.95 + 1G > A)突变引起的α -地中海贫血及其与其他形式的地中海贫血或血红蛋白病的组合
ααIVSI-1(AGGT> AGAT)突变通常在常规的地中海贫血检测中被忽略,因为它在杂合个体中具有轻微或不存在的病理,以及它与可导致可变表型的调节剂的相互作用,特别是在β-地中海贫血(β-thal)和血红蛋白E (HbE)携带者中。本研究采用靶向下一代测序(NGS)技术分析了泰国北部地区ααIVSI-1(AGGT> AGAT)突变。Hb分析采用HPLC和/或CE法。采用高分辨率熔解实时PCR检测α-thal-1—SEA、—Thai和—Chiang Rai型缺失,采用常规gap-PCR检测α-thal-2 (-α3.7和-α4.2)缺失。利用针对HBA1、HBA2和HBB基因编码区的NGS面板进一步研究地中海贫血基因型。ααIVSI-1(AGGT> AGAT)突变被常规地中海贫血诊断方法误诊。NGS结果显示,1107份(0.63%)血样中有7份(3份来自缅甸,4份来自泰国)ααIVSI-1(AGGT> AGAT)突变为杂合子,出现在5个不同的基因型中。临床和血液学特征因其组合形式而异。本研究中使用的靶向NGS分析是一种很有前途的基因检测方法,用于鉴定罕见的珠蛋白基因突变。它在地中海贫血筛查和遗传咨询方面显示出特别的前景。
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
CiteScore
1.70
自引率
0.00%
发文量
82
审稿时长
>12 weeks
期刊介绍: Indian Journal of Hematology and Blood Transfusion is a medium for propagating and exchanging ideas within the medical community. It publishes peer-reviewed articles on a variety of aspects of clinical hematology, laboratory hematology and hemato-oncology. The journal exists to encourage scientific investigation in the study of blood in health and in disease; to promote and foster the exchange and diffusion of knowledge relating to blood and blood-forming tissues; and to provide a forum for discussion of hematological subjects on a national scale. The Journal is the official publication of The Indian Society of Hematology & Blood Transfusion.
×
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:604180095
Book学术官方微信