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 , Pernille Axél Gregersen , Trine Østergaard Nielsen , Line Graven Lyngdorf , Christine Kroer Nielsen , Casper Kruse , Michael Bayat , Philippe M. Campeau , 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 , Pernille Axél Gregersen , Trine Østergaard Nielsen , Line Graven Lyngdorf , Christine Kroer Nielsen , Casper Kruse , Michael Bayat , Philippe M. Campeau , 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}
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.
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.