{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T14:54:30Z","timestamp":1793717670107,"version":"4.6.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"\n Objective<\/jats:title>\n \n ADGRV1<\/jats:italic>\n gene encodes adhesion G protein-coupled receptor-V1 that is involved in synaptic function.\n ADGRV1<\/jats:italic>\n mutations are associated with audio-visual disorders. Although previous experimental studies suggested that\n ADGRV1<\/jats:italic>\n variants were associated with epilepsy, clinical evidence is limited and the phenotype spectrum is to be defined.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Trio-based targeting sequencing was performed in a cohort of 101 cases with febrile seizure (FS) and epilepsy with antecedent FS. Protein modeling was used to assess the damaging effects of variants. The genotype-phenotype correlations of the\n ADGRV1<\/jats:italic>\n variants in epilepsy and audio-visual disorders were analyzed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n ADGRV1<\/jats:italic>\n variants were identified in nine unrelated cases (8.91%), including two heterozygous frameshift variants, six heterozygous missense variants, and a pair of compound heterozygous variants. These variants presented a statistically higher frequency in this cohort than that in control populations. Most missense variants were located at CalX-\u03b2 motifs and changed the hydrogen bonds. These variants were inherited from the asymptomatic parents, indicating an incomplete penetrance. We also identified\n SCN1A<\/jats:italic>\n variants in 25 unrelated cases (24.75%) and\n SCN9A<\/jats:italic>\n variants in 3 unrelated cases (2.97%) in this cohort. Contrary to\n SCN1A<\/jats:italic>\n variant-associated epilepsy that revealed seizure was aggravated by sodium channel blockers,\n ADGRV1<\/jats:italic>\n variants were associated with mild epilepsy with favorable responses to antiepileptic drugs. The patients denied problems with audio-visual-vestibular abilities in daily life. However, audio-visual tests revealed auditory and visual impairment in the patient with compound heterozygous variants, auditory or vestibular impairment in the patients with heterozygous frameshift, or hydrogen-bond changed missense variants but no abnormalities in the patients with missense variants without hydrogen-bond changes. Previously reported\n ADGRV1<\/jats:italic>\n variants that were associated with audio-visual disorders were mostly biallelic\/destructive variants, which were significantly more frequent in the severe phenotype of audio-visual disorders (Usher syndrome 2) than in other mild phenotypes. In contrast, the variants identified in epilepsy were monoallelic, missense mainly located at CalX-\u03b2, or affected isoforms VLGR1b\/1c.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n \n ADGRV1<\/jats:italic>\n is potentially associated with FS-related epilepsy as a susceptibility gene. The genotype, submolecular implication, isoforms, and damaging severity of the variants explained the phenotypical variations.\n ADGRV1<\/jats:italic>\n variant-associated FS\/epilepsy presented favorable responses to antiepileptic drugs, implying a clinical significance.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fnmol.2022.864074","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T08:22:27Z","timestamp":1655972547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["ADGRV1 Variants in Febrile Seizures\/Epilepsy With Antecedent Febrile Seizures and Their Associations With Audio-Visual Abnormalities"],"prefix":"10.3389","volume":"15","author":[{"given":"Peng","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingmei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hankui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongxiang","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1006\/jmbi.1997.1510","article-title":"Merging extracellular domains: fold prediction for laminin G-like and amino-terminal thrombospondin-like modules based on homology to pentraxins","volume":"275","author":"Beckmann","year":"1998","journal-title":"J. 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