A Novel UPF1 Variant Associated With a Rare UPF1-Related Neurodevelopmental Disorder.

IF 2.9 3区 医学 Q2 GENETICS & HEREDITY
Zeynep Tümer, Jonas Dalsberg, Gitte Rønde, Jesper Kiehn Sørensen, Elsebet Østergaard
{"title":"A Novel UPF1 Variant Associated With a Rare UPF1-Related Neurodevelopmental Disorder.","authors":"Zeynep Tümer, Jonas Dalsberg, Gitte Rønde, Jesper Kiehn Sørensen, Elsebet Østergaard","doi":"10.1111/cge.14735","DOIUrl":null,"url":null,"abstract":"<p><p>Nonsense-mediated mRNA decay (NMD) plays a crucial role in degrading aberrant transcripts with premature termination codons, with the Up-frameshift (UPF) protein family-UPF1, UPF2, and UPF3A/UPF3B-being vital components of this machinery. While several variants in genes encoding UPF2 and UPF3A/3B have been associated with neurodevelopmental disorders, only three germline UPF1 variants have been reported to date. Here, we report a male patient with a de novo missense variant, p.(Ala526Thr), in a highly conserved helicase motif of UPF1. The patient presented with moderate intellectual disability (ID), atypical autism, attention deficit hyperactivity disorder (ADHD), and behavioral disturbances. The common features observed among the four patients with UPF1 variants are moderate to severe ID and developmental delays in motor and verbal skills. A comparison across the disorders related to the UPF genes suggests that neurodevelopmental delay, including ID and impaired verbal skills, is a common feature, and these disorders may collectively be referred to as UPF-related neurodevelopmental disorders (NDDs). ADHD, autism, seizures, hypotonia, and non-specific dysmorphic features are also reported in some patients, suggesting that these disorders can be classified as non-specific intellectual disability syndromes. However, further studies are necessary to elucidate genotype-phenotype correlations and the molecular mechanisms underlying these rare disorders, particularly those related to UPF1.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cge.14735","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Nonsense-mediated mRNA decay (NMD) plays a crucial role in degrading aberrant transcripts with premature termination codons, with the Up-frameshift (UPF) protein family-UPF1, UPF2, and UPF3A/UPF3B-being vital components of this machinery. While several variants in genes encoding UPF2 and UPF3A/3B have been associated with neurodevelopmental disorders, only three germline UPF1 variants have been reported to date. Here, we report a male patient with a de novo missense variant, p.(Ala526Thr), in a highly conserved helicase motif of UPF1. The patient presented with moderate intellectual disability (ID), atypical autism, attention deficit hyperactivity disorder (ADHD), and behavioral disturbances. The common features observed among the four patients with UPF1 variants are moderate to severe ID and developmental delays in motor and verbal skills. A comparison across the disorders related to the UPF genes suggests that neurodevelopmental delay, including ID and impaired verbal skills, is a common feature, and these disorders may collectively be referred to as UPF-related neurodevelopmental disorders (NDDs). ADHD, autism, seizures, hypotonia, and non-specific dysmorphic features are also reported in some patients, suggesting that these disorders can be classified as non-specific intellectual disability syndromes. However, further studies are necessary to elucidate genotype-phenotype correlations and the molecular mechanisms underlying these rare disorders, particularly those related to UPF1.

一种新的UPF1变异与罕见的UPF1相关神经发育障碍相关。
无义介导的mRNA衰变(NMD)在降解带有过早终止密码子的异常转录本中起着至关重要的作用,而上移码(UPF)蛋白家族——upf1、UPF2和UPF3A/ upf3b是这一机制的重要组成部分。虽然编码UPF2和UPF3A/3B基因的几个变异与神经发育障碍有关,但迄今为止仅报道了三种种系UPF1变异。在这里,我们报告了一名男性患者,在UPF1的高度保守的解旋酶基序中有一个新的错义变体p.(Ala526Thr)。患者表现为中度智力障碍(ID)、非典型自闭症、注意缺陷多动障碍(ADHD)和行为障碍。在4例UPF1变异患者中观察到的共同特征是中度至重度ID和运动和语言技能的发育迟缓。与UPF基因相关的疾病的比较表明,神经发育迟缓,包括ID和语言技能受损,是一个共同的特征,这些疾病可以统称为UPF相关神经发育障碍(ndd)。ADHD、自闭症、癫痫发作、低张力和非特异性畸形特征也在一些患者中被报道,这表明这些疾病可以被归类为非特异性智力残疾综合征。然而,需要进一步的研究来阐明基因型-表型相关性和这些罕见疾病的分子机制,特别是与UPF1相关的疾病。
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
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
×
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