@article {Happe603作者={汉娜c没说完Lynette g . Sadleir和马修·泽梅尔Guillem de Valles-Ib {\ '} {\ ~ n} ez和迈克尔·S·希尔德布兰德和阿林McConkie-Rosell和玛丽麦当劳Halie可能和特里斯坦金沙Vimla Aggarwal克里斯托弗长者和盖Feyma艾伦到了和Rikke S M {\ o}会和克里斯蒂娜·d·风阁Jens Erik陡崖尼尔森和安妮塔n达塔和凯萨琳·M·戈尔曼和玛丽·d·金和纳塔莉亚·d·Linhares芭芭拉·k·伯顿和安德里亚·帕拉斯西安Ellard和朱莉娅·兰金和安居Shukla Purvi Majethia和罗里j . Olson和恋人Muthusamy和丽莎a Schimmenti基斯Starnes和露西Sedl {\ '} {\ v c} kov {\ '}, Katalin {\ v S} {\ v e} rbov {\ ' t}和马克{\ ' e} ta六世{\ v c} kov{\ '},佩特拉La {\ v S} {\ v S} uthov{\ '}和阿勒娜Jahodov{\ '}和布伦达·e·波特和娜塔莉Couque埃斯特尔科林和Cl {\ ' e}表示“状态”Prouteau柯琳夹头和托马斯Smol Roseline Caumes与芙蓉Vansenne弗朗西斯卡Bisulli和劳拉Licchetta和理查德·人艾琳·托提和基McWalter和理查德·韦伯斯特和伊丽莎白·e·杰拉德和局长Gaetan Lesca皮埃尔Szepetowski英格丽·e·雅伯和希瑟·c·Mefford吉玛l . Carvill} title ={神经发育和癫痫表型患者错义Voltage-Sensing和孔隙域的变异KCNH5},体积={100}={6},页面= {e603——e615} = {2023}, doi = {10.1212 / WNL。出版商0000000000201492}= {Wolters Kluwer健康,公司代表美国神经病学学会},文摘={背景和目标KCNH5编码电压门控钾通道EAG2 / Kv10.2。首页我们旨在描绘神经发育和癫痫表型频谱与新创KCNH5变异有关。方法筛选893个个体发育和癫痫脑病KCNH5变体使用目标或外显子组测序。额外的个人KCNH5变异是通过国际合作来确定的。临床病史、脑电图和成像数据进行了分析;癫痫发作类型和症状分类。我们包括3以前公布的个人包括额外的表型的细节。结果我们报告一群17例,其中包括9 p与复发性新创错义变体。Arg327His 4 p与复发性错义变体。错义变异Arg333His和4额外的小说。变体都位于或接近功能关键voltage-sensing或孔隙域,在一般人群缺席,归类为致病性或可能致病的美国大学医学遗传学和基因组学标准。 All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death.Discussion We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.ACMG=American College of Medical Genetics and Genomics; DEE=developmental and epileptic encephalopathy; EAG=ether-a-go-go; ID=intellectual disability; GOF=gain of function; MIP=molecular inversion probe; NDD=neurodevelopmental disorder; VUS=variants of uncertain significance}, issn = {0028-3878}, URL = {//www.ez-admanager.com/content/100/6/e603}, eprint = {//www.ez-admanager.com/content/100/6/e603.full.pdf}, journal = {Neurology} }