Unusual Causes of β Thalassemia Trait: Discovery of another Three Novel SUPT5H Variants.

IF 1.2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nik Fatma Fairuz Nik Mohd Hasan, Ahlem Achour, Tamara Koopmann, Adriaan van Gammeren, Joep van der Leeuw, Huib Ceelie, Daniel Stieber, Frank Baas, Cornelis L Harteveld
{"title":"Unusual Causes of β Thalassemia Trait: Discovery of another Three Novel <i>SUPT5H</i> Variants.","authors":"Nik Fatma Fairuz Nik Mohd Hasan, Ahlem Achour, Tamara Koopmann, Adriaan van Gammeren, Joep van der Leeuw, Huib Ceelie, Daniel Stieber, Frank Baas, Cornelis L Harteveld","doi":"10.1080/03630269.2025.2484230","DOIUrl":null,"url":null,"abstract":"<p><p>Beta (β) thalassemia is an inherited disorder that occurs following mutations or deletions in the β globin gene. Rarely, it is caused by variants in genes coding for erythroid transcriptional factors or trans-acting factors. Here, we report three novel variants of <i>SUPT5H</i> revealed by next generation sequencing. This, gene has been progressively acknowledged as a mimicker of β thalassemia trait in two independent individuals and one family. These individuals have the same features, including hypochromic microcytic indices, increased Hb A<sub>2</sub> levels, without mutations in the β globin gene. The three novel <i>SUPT5H</i> variants identified in this study (c.1168_1169del, c.2688del and c.307+1G>A) are frameshift variants leading to a premature stop codon or an intronic variant predicted to alter the splice site consensus sequence by <i>in silico</i> software. All three variants are characterized as Loss-of-Function variants either by generating a truncated protein or haplo-insufficiency due to nonsense-mediated decay. These findings confirm the general observation that most variants in <i>SUPT5H</i> associated with a β thalassemia trait phenotype are Loss-of-Function variants. This gene should be considered as a potential target gene in the genetic diagnosis of any unsolved cases of increased HbA<sub>2</sub> and unexplained inconsistency of phenotype and genotype of β thalassemia intermedia.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-4"},"PeriodicalIF":1.2000,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hemoglobin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03630269.2025.2484230","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

Beta (β) thalassemia is an inherited disorder that occurs following mutations or deletions in the β globin gene. Rarely, it is caused by variants in genes coding for erythroid transcriptional factors or trans-acting factors. Here, we report three novel variants of SUPT5H revealed by next generation sequencing. This, gene has been progressively acknowledged as a mimicker of β thalassemia trait in two independent individuals and one family. These individuals have the same features, including hypochromic microcytic indices, increased Hb A2 levels, without mutations in the β globin gene. The three novel SUPT5H variants identified in this study (c.1168_1169del, c.2688del and c.307+1G>A) are frameshift variants leading to a premature stop codon or an intronic variant predicted to alter the splice site consensus sequence by in silico software. All three variants are characterized as Loss-of-Function variants either by generating a truncated protein or haplo-insufficiency due to nonsense-mediated decay. These findings confirm the general observation that most variants in SUPT5H associated with a β thalassemia trait phenotype are Loss-of-Function variants. This gene should be considered as a potential target gene in the genetic diagnosis of any unsolved cases of increased HbA2 and unexplained inconsistency of phenotype and genotype of β thalassemia intermedia.

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