Genetic evidence for predisposition to acute leukemias due to a missense mutation (p.Ser518Arg) in ZAP70 kinase: a case-control study.

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY BMC Medical Genomics Pub Date : 2024-08-07 DOI:10.1186/s12920-024-01961-0
Khalil Khashei Varnamkhasti, Samire Khashei Varnamkhasti, Atefeh Shahrouzian, Masoomeh Rahimzadeh, Leila Naeimi, Behrouz Naeimi, Sirous Naeimi
{"title":"Genetic evidence for predisposition to acute leukemias due to a missense mutation (p.Ser518Arg) in ZAP70 kinase: a case-control study.","authors":"Khalil Khashei Varnamkhasti, Samire Khashei Varnamkhasti, Atefeh Shahrouzian, Masoomeh Rahimzadeh, Leila Naeimi, Behrouz Naeimi, Sirous Naeimi","doi":"10.1186/s12920-024-01961-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The apparent lack of additional missense mutations data on mixed-phenotype leukemia is noteworthy. Single amino acid substitution by these non-synonymous single nucleotide variations can be related to many pathological conditions and may influence susceptibility to disease. This case-control study aimed to unravel whether the ZAP70 missense variant (rs104893674 (C > A)) underpinning mixed-phenotype leukemia.</p><p><strong>Methods: </strong>The rs104893674 was genotyped in clients who were mixed-phenotype acute leukemia-, acute lymphoblastic leukemia- and acute myeloid leukemia-positive and matched healthy controls, which have been referred to all major urban hospitals from multiple provinces of country- wide, IRAN, from February 11' 2019 to June 10' 2023, by amplification refractory mutation system-polymerase chain reaction method. Direct sequencing for rs104893674 of the ZAP70 gene was performed in a 3130 Genetic Analyzer.</p><p><strong>Results: </strong>We found that the AC genotype of individuals with A allele at this polymorphic site (heterozygous variant-type) contribute to the genetic susceptibility to acute leukemia of both forms, acute myeloid leukemia and acute lymphoblastic leukemia as well as with a mixed phenotype. In other words, the ZAP70 missense variant (rs104893674 (C > A)) increases susceptibility of distinct cell populations of different (myeloid and lymphoid) lineages to exhibiting cancer phenotype. The results were all consistent with genotype data obtained using a direct DNA sequencing technique.</p><p><strong>Conclusion: </strong>Of special interest are pathogenic missense mutations, since they generate variants that cause specific molecular phenotypes through protein destabilization. Overall, we discovered that the rs104893674 (C > A) variant chance in causing mixed-phenotype leukemia is relatively high.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308335/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Medical Genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12920-024-01961-0","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: The apparent lack of additional missense mutations data on mixed-phenotype leukemia is noteworthy. Single amino acid substitution by these non-synonymous single nucleotide variations can be related to many pathological conditions and may influence susceptibility to disease. This case-control study aimed to unravel whether the ZAP70 missense variant (rs104893674 (C > A)) underpinning mixed-phenotype leukemia.

Methods: The rs104893674 was genotyped in clients who were mixed-phenotype acute leukemia-, acute lymphoblastic leukemia- and acute myeloid leukemia-positive and matched healthy controls, which have been referred to all major urban hospitals from multiple provinces of country- wide, IRAN, from February 11' 2019 to June 10' 2023, by amplification refractory mutation system-polymerase chain reaction method. Direct sequencing for rs104893674 of the ZAP70 gene was performed in a 3130 Genetic Analyzer.

Results: We found that the AC genotype of individuals with A allele at this polymorphic site (heterozygous variant-type) contribute to the genetic susceptibility to acute leukemia of both forms, acute myeloid leukemia and acute lymphoblastic leukemia as well as with a mixed phenotype. In other words, the ZAP70 missense variant (rs104893674 (C > A)) increases susceptibility of distinct cell populations of different (myeloid and lymphoid) lineages to exhibiting cancer phenotype. The results were all consistent with genotype data obtained using a direct DNA sequencing technique.

Conclusion: Of special interest are pathogenic missense mutations, since they generate variants that cause specific molecular phenotypes through protein destabilization. Overall, we discovered that the rs104893674 (C > A) variant chance in causing mixed-phenotype leukemia is relatively high.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
ZAP70激酶中一个错义突变(p.Ser518Arg)导致易患急性白血病的遗传学证据:一项病例对照研究。
背景:值得注意的是,混合表型白血病明显缺乏额外的错义突变数据。这些非同义单核苷酸变异的单氨基酸置换可能与许多病理情况有关,并可能影响对疾病的易感性。这项病例对照研究旨在揭示ZAP70错义变异(rs104893674 (C > A))是否是混合表型白血病的基础:方法:在2019年2月11日至2023年6月10日期间,通过扩增难治性突变系统聚合酶链反应方法,对转诊至伊朗全国多个省份所有主要城市医院的混合表型急性白血病、急性淋巴细胞白血病和急性髓性白血病阳性患者及匹配的健康对照者进行rs104893674基因分型。在 3130 基因分析仪上对 ZAP70 基因的 rs104893674 进行了直接测序:结果:我们发现,在该多态位点上具有 A 等位基因(杂合子变异型)的个体的 AC 基因型是急性髓性白血病和急性淋巴细胞白血病这两种急性白血病以及混合表型的遗传易感性因素之一。换句话说,ZAP70 错义变体(rs104893674 (C > A))增加了不同(髓系和淋巴系)细胞群对癌症表型的易感性。结果与使用直接 DNA 测序技术获得的基因型数据一致:结论:致病性错义突变特别值得关注,因为它们产生的变体会通过破坏蛋白质的稳定性而导致特定的分子表型。总之,我们发现 rs104893674(C > A)变异导致混合型白血病的几率相对较高。
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 去求助
来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
期刊最新文献
The signature of SARS-CoV-2-related genes predicts the immune therapeutic response and prognosis in breast cancer. Association between venous thromboembolism and atrial fibrillation: a Mendelian randomization study. New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis. RNA-seq validation of microRNA expression signatures for precision melanoma diagnosis and prognostic stratification. The Toll-like receptor 4 antagonist TAK-242 in combination with sodium hyaluronate alleviates postoperative abdominal adhesion in a mouse model.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1