一种传染性致病性KAT6B变异的可变表达性

IF 1.6 4区 医学 Q3 GENETICS & HEREDITY
Ninna Bager Rasmussen , Pernille Axél Gregersen , Trine Østergaard Nielsen , Line Graven Lyngdorf , Christine Kroer Nielsen , Casper Kruse , Michael Bayat , Philippe M. Campeau , Anne Skakkebæk
{"title":"一种传染性致病性KAT6B变异的可变表达性","authors":"Ninna Bager Rasmussen ,&nbsp;Pernille Axél Gregersen ,&nbsp;Trine Østergaard Nielsen ,&nbsp;Line Graven Lyngdorf ,&nbsp;Christine Kroer Nielsen ,&nbsp;Casper Kruse ,&nbsp;Michael Bayat ,&nbsp;Philippe M. Campeau ,&nbsp;Anne Skakkebæk","doi":"10.1016/j.ejmg.2025.105020","DOIUrl":null,"url":null,"abstract":"<div><div>Pathogenic variants in <em>KAT6B</em> (Lysine acetyltransferase 6B) are associated with two clinically overlapping autosomal dominant disorders Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM <span><span>603736</span><svg><path></path></svg></span>), and Genitopatellar syndrome (GPS) (OMIM <span><span>606170</span><svg><path></path></svg></span>). More recently, the clinical spectrum of <em>KAT6B</em> disorders has expanded and <em>KAT6B</em> disorders have been suggested to consist of a spectrum of disorders with intermediate and overlapping clinical manifestations. Pathogenic variants in <em>KAT6B</em> mainly occur <em>de novo</em>, with only 3 reports of inherited variants. Here, we describe clinical and molecular findings in a three-generation Danish family with a segregating, previously unreported, pathogenic <em>KAT6B</em> variant. The variant is associated with a phenotype not otherwise specified (neither SBBYSS nor GPS) and with variable expressivity, adding further evidence that <em>KAT6B</em> disorders should be seen as a broad clinical spectrum. Furthermore, we highlight the existence of intra-familial variability and that pathogenic variants in <em>KAT6B</em> can be inherited from mildly affected parents.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"76 ","pages":"Article 105020"},"PeriodicalIF":1.6000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Variable expressivity of a transmitted pathogenic KAT6B variant\",\"authors\":\"Ninna Bager Rasmussen ,&nbsp;Pernille Axél Gregersen ,&nbsp;Trine Østergaard Nielsen ,&nbsp;Line Graven Lyngdorf ,&nbsp;Christine Kroer Nielsen ,&nbsp;Casper Kruse ,&nbsp;Michael Bayat ,&nbsp;Philippe M. Campeau ,&nbsp;Anne Skakkebæk\",\"doi\":\"10.1016/j.ejmg.2025.105020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Pathogenic variants in <em>KAT6B</em> (Lysine acetyltransferase 6B) are associated with two clinically overlapping autosomal dominant disorders Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM <span><span>603736</span><svg><path></path></svg></span>), and Genitopatellar syndrome (GPS) (OMIM <span><span>606170</span><svg><path></path></svg></span>). More recently, the clinical spectrum of <em>KAT6B</em> disorders has expanded and <em>KAT6B</em> disorders have been suggested to consist of a spectrum of disorders with intermediate and overlapping clinical manifestations. Pathogenic variants in <em>KAT6B</em> mainly occur <em>de novo</em>, with only 3 reports of inherited variants. Here, we describe clinical and molecular findings in a three-generation Danish family with a segregating, previously unreported, pathogenic <em>KAT6B</em> variant. The variant is associated with a phenotype not otherwise specified (neither SBBYSS nor GPS) and with variable expressivity, adding further evidence that <em>KAT6B</em> disorders should be seen as a broad clinical spectrum. Furthermore, we highlight the existence of intra-familial variability and that pathogenic variants in <em>KAT6B</em> can be inherited from mildly affected parents.</div></div>\",\"PeriodicalId\":11916,\"journal\":{\"name\":\"European journal of medical genetics\",\"volume\":\"76 \",\"pages\":\"Article 105020\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European journal of medical genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1769721225000278\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of medical genetics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1769721225000278","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

摘要

KAT6B(赖氨酸乙酰转移酶6B)的致病变异与两种临床重叠的常染色体显性遗传病sayer - barber - biesecker - young - simpson综合征(SBBYSS) (OMIM 603736)和生殖器髌骨综合征(GPS) (OMIM 606170)相关。最近,KAT6B疾病的临床谱已经扩大,KAT6B疾病被认为是由一系列具有中间和重叠临床表现的疾病组成的。KAT6B的致病变异主要发生于新生,仅有3例遗传变异报告。在这里,我们描述了一个丹麦三代家族的临床和分子发现,该家族具有分离性,以前未报道的致病性KAT6B变异。该变体与其他未指定的表型(既不是SBBYSS也不是GPS)相关,并且具有可变的表达性,进一步证明KAT6B疾病应被视为广泛的临床谱系。此外,我们强调了家族内变异的存在,KAT6B的致病变异可以从轻度患病的父母那里遗传。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Variable expressivity of a transmitted pathogenic KAT6B variant
Pathogenic variants in KAT6B (Lysine acetyltransferase 6B) are associated with two clinically overlapping autosomal dominant disorders Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM 603736), and Genitopatellar syndrome (GPS) (OMIM 606170). More recently, the clinical spectrum of KAT6B disorders has expanded and KAT6B disorders have been suggested to consist of a spectrum of disorders with intermediate and overlapping clinical manifestations. Pathogenic variants in KAT6B mainly occur de novo, with only 3 reports of inherited variants. Here, we describe clinical and molecular findings in a three-generation Danish family with a segregating, previously unreported, pathogenic KAT6B variant. The variant is associated with a phenotype not otherwise specified (neither SBBYSS nor GPS) and with variable expressivity, adding further evidence that KAT6B disorders should be seen as a broad clinical spectrum. Furthermore, we highlight the existence of intra-familial variability and that pathogenic variants in KAT6B can be inherited from mildly affected parents.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
4.10
自引率
0.00%
发文量
193
审稿时长
66 days
期刊介绍: The European Journal of Medical Genetics (EJMG) is a peer-reviewed journal that publishes articles in English on various aspects of human and medical genetics and of the genetics of experimental models. Original clinical and experimental research articles, short clinical reports, review articles and letters to the editor are welcome on topics such as : • Dysmorphology and syndrome delineation • Molecular genetics and molecular cytogenetics of inherited disorders • Clinical applications of genomics and nextgen sequencing technologies • Syndromal cancer genetics • Behavioral genetics • Community genetics • Fetal pathology and prenatal diagnosis • Genetic counseling.
×
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