Wenting Lei, Yurong Xiong, Yongyuan Shi, Lingling Song, Jing Xiang, Fan Yang, Xi Wu, Huifeng Wang, Maoqiang Tian
{"title":"ADGRL1 变体:从发育性和癫痫性脑病到伴发热性癫痫发作的遗传性癫痫加。","authors":"Wenting Lei, Yurong Xiong, Yongyuan Shi, Lingling Song, Jing Xiang, Fan Yang, Xi Wu, Huifeng Wang, Maoqiang Tian","doi":"10.1111/dmcn.16005","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>To expand the phenotypic spectrum of ADGRL1 and explore the correlation between epilepsy and the ADGRL1 genotype.</p><p><strong>Method: </strong>We performed whole-exome sequencing in a cohort of 115 families (including 195 males and 150 females) with familial febrile seizure or epilepsy with unexplained aetiology. The damaging effects of variants was predicted using protein modelling and multiple in silico tools. All reported patients with ADGRL1 pathogenic variants were analysed.</p><p><strong>Results: </strong>One new ADGRL1 variant (p.Pro753Leu) was identified in one family with genetic epilepsy with febrile seizures. Further analysis of 12 ADGRL1 variants in 16 patients revealed that six patients had epilepsy. Epilepsy types ranged from early-onset epileptic encephalopathy to genetic epilepsy with febrile seizures plus (GEFS+). All four variants associated with epilepsy were located in the non-helix or sheet region of ADGRL1. Three of the four epilepsy-associated variants were missense variants. Thus, all three variants located in the G-protein-coupled receptor autoproteolytic-inducing domain exhibited epilepsy.</p><p><strong>Interpretation: </strong>We found one new missense variant of ADGRL1 in one family with GEFS+. ADGRL1 may be a potential candidate or susceptibility gene for epilepsy. ADGRL1-associated epilepsy ranged from benign GEFS+ to severe epileptic encephalopathy; the genotypes and variant locations may help explain the phenotypic heterogeneity of patients with the ADGRL1 variant.</p>","PeriodicalId":50587,"journal":{"name":"Developmental Medicine and Child Neurology","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ADGRL1 variants: From developmental and epileptic encephalopathy to genetic epilepsy with febrile seizures plus.\",\"authors\":\"Wenting Lei, Yurong Xiong, Yongyuan Shi, Lingling Song, Jing Xiang, Fan Yang, Xi Wu, Huifeng Wang, Maoqiang Tian\",\"doi\":\"10.1111/dmcn.16005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>To expand the phenotypic spectrum of ADGRL1 and explore the correlation between epilepsy and the ADGRL1 genotype.</p><p><strong>Method: </strong>We performed whole-exome sequencing in a cohort of 115 families (including 195 males and 150 females) with familial febrile seizure or epilepsy with unexplained aetiology. The damaging effects of variants was predicted using protein modelling and multiple in silico tools. All reported patients with ADGRL1 pathogenic variants were analysed.</p><p><strong>Results: </strong>One new ADGRL1 variant (p.Pro753Leu) was identified in one family with genetic epilepsy with febrile seizures. Further analysis of 12 ADGRL1 variants in 16 patients revealed that six patients had epilepsy. Epilepsy types ranged from early-onset epileptic encephalopathy to genetic epilepsy with febrile seizures plus (GEFS+). All four variants associated with epilepsy were located in the non-helix or sheet region of ADGRL1. Three of the four epilepsy-associated variants were missense variants. Thus, all three variants located in the G-protein-coupled receptor autoproteolytic-inducing domain exhibited epilepsy.</p><p><strong>Interpretation: </strong>We found one new missense variant of ADGRL1 in one family with GEFS+. ADGRL1 may be a potential candidate or susceptibility gene for epilepsy. ADGRL1-associated epilepsy ranged from benign GEFS+ to severe epileptic encephalopathy; the genotypes and variant locations may help explain the phenotypic heterogeneity of patients with the ADGRL1 variant.</p>\",\"PeriodicalId\":50587,\"journal\":{\"name\":\"Developmental Medicine and Child Neurology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-06-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Developmental Medicine and Child Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/dmcn.16005\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental Medicine and Child Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dmcn.16005","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
ADGRL1 variants: From developmental and epileptic encephalopathy to genetic epilepsy with febrile seizures plus.
Aim: To expand the phenotypic spectrum of ADGRL1 and explore the correlation between epilepsy and the ADGRL1 genotype.
Method: We performed whole-exome sequencing in a cohort of 115 families (including 195 males and 150 females) with familial febrile seizure or epilepsy with unexplained aetiology. The damaging effects of variants was predicted using protein modelling and multiple in silico tools. All reported patients with ADGRL1 pathogenic variants were analysed.
Results: One new ADGRL1 variant (p.Pro753Leu) was identified in one family with genetic epilepsy with febrile seizures. Further analysis of 12 ADGRL1 variants in 16 patients revealed that six patients had epilepsy. Epilepsy types ranged from early-onset epileptic encephalopathy to genetic epilepsy with febrile seizures plus (GEFS+). All four variants associated with epilepsy were located in the non-helix or sheet region of ADGRL1. Three of the four epilepsy-associated variants were missense variants. Thus, all three variants located in the G-protein-coupled receptor autoproteolytic-inducing domain exhibited epilepsy.
Interpretation: We found one new missense variant of ADGRL1 in one family with GEFS+. ADGRL1 may be a potential candidate or susceptibility gene for epilepsy. ADGRL1-associated epilepsy ranged from benign GEFS+ to severe epileptic encephalopathy; the genotypes and variant locations may help explain the phenotypic heterogeneity of patients with the ADGRL1 variant.
期刊介绍:
Wiley-Blackwell is pleased to publish Developmental Medicine & Child Neurology (DMCN), a Mac Keith Press publication and official journal of the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) and the British Paediatric Neurology Association (BPNA).
For over 50 years, DMCN has defined the field of paediatric neurology and neurodisability and is one of the world’s leading journals in the whole field of paediatrics. DMCN disseminates a range of information worldwide to improve the lives of disabled children and their families. The high quality of published articles is maintained by expert review, including independent statistical assessment, before acceptance.