Molecular and Clinical Insights into KMT2E-Related O'Donnell-Luria-Rodan Syndrome in a Novel Patient Cohort.

IF 1.6 4区 医学 Q3 GENETICS & HEREDITY European journal of medical genetics Pub Date : 2024-12-19 DOI:10.1016/j.ejmg.2024.104990
Davide Vecchio, Filippo M Panfili, Marina Macchiaiolo, Maria Lisa Dentici, Marina Trivisano, Carolina Benitez Medina, Rossella Capolino, Emanuela Salzano, Fabiana Cortellessa, Martina Busè, Antonio Pantaleo, Dario Cocciadiferro, Michaela V Gonfiantini, Marcello Niceta, Angela De Dominicis, Nicola Specchio, Maria Piccione, Maria Cristina Digilio, Marco Tartaglia, Antonio Novelli, Andrea Bartuli
{"title":"Molecular and Clinical Insights into KMT2E-Related O'Donnell-Luria-Rodan Syndrome in a Novel Patient Cohort.","authors":"Davide Vecchio, Filippo M Panfili, Marina Macchiaiolo, Maria Lisa Dentici, Marina Trivisano, Carolina Benitez Medina, Rossella Capolino, Emanuela Salzano, Fabiana Cortellessa, Martina Busè, Antonio Pantaleo, Dario Cocciadiferro, Michaela V Gonfiantini, Marcello Niceta, Angela De Dominicis, Nicola Specchio, Maria Piccione, Maria Cristina Digilio, Marco Tartaglia, Antonio Novelli, Andrea Bartuli","doi":"10.1016/j.ejmg.2024.104990","DOIUrl":null,"url":null,"abstract":"<p><p>O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant neurodevelopmental disorder mainly characterized by global development delay/intellectual disability, white matter abnormalities, and behavioral manifestations. It is caused by pathogenic variants in the KMT2E gene. Here we report seven new patients with loss-of-function KMT2E variants, six harboring frameshift/nonsense changes, and one with a 7q22.3 microdeletion encompassing the entire gene-locus. We further characterize both the clinical phenotype as well as its associated pathogenic variants' spectrum providing new information on sex-related phenotype distribution, according to the variant groups. We also highlight different epilepsy phenotype-genotype correlation with preferential association of generalized epilepsy and/or developmental and epileptic encephalopathy with missense pathogenic variants and focal epilepsy, childhood absence epilepsy and/or febrile seizures with pathogenic truncating variants and structural rearrangements. By a systematic review of the previously reported series, we also discuss previously unappreciated findings, including progressive macrocephaly, apraxia, and higher risk of bone fractures.</p>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":" ","pages":"104990"},"PeriodicalIF":1.6000,"publicationDate":"2024-12-19","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://doi.org/10.1016/j.ejmg.2024.104990","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

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant neurodevelopmental disorder mainly characterized by global development delay/intellectual disability, white matter abnormalities, and behavioral manifestations. It is caused by pathogenic variants in the KMT2E gene. Here we report seven new patients with loss-of-function KMT2E variants, six harboring frameshift/nonsense changes, and one with a 7q22.3 microdeletion encompassing the entire gene-locus. We further characterize both the clinical phenotype as well as its associated pathogenic variants' spectrum providing new information on sex-related phenotype distribution, according to the variant groups. We also highlight different epilepsy phenotype-genotype correlation with preferential association of generalized epilepsy and/or developmental and epileptic encephalopathy with missense pathogenic variants and focal epilepsy, childhood absence epilepsy and/or febrile seizures with pathogenic truncating variants and structural rearrangements. By a systematic review of the previously reported series, we also discuss previously unappreciated findings, including progressive macrocephaly, apraxia, and higher risk of bone fractures.

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
求助全文
约1分钟内获得全文 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.
期刊最新文献
NONO-related X-linked intellectual disability syndrome: further clinical and molecular delineation. Catalogue of inherited autosomal recessive disorders found amongst the Roma population of Europe. CHD3-related Snijders Blok-Campeau syndrome with Spastic Paraplegia, Ataxia, and Situs Inversus. Heterozygous Inversion on Chromosome 17 involving PAFAH1B1 Detected by Whole Genome Sequencing in a Patient Suffering from Pachygyria. Molecular and Clinical Insights into KMT2E-Related O'Donnell-Luria-Rodan Syndrome in a Novel Patient Cohort.
×
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