{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T01:04:20Z","timestamp":1784077460651,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic\u2010related migration disorder. It has been attributed to loss\u2010of\u2010function of the ADGRG1 gene, which encodes an adhesion G protein\u2010coupled receptor, ADGRG1\/GPR56. We report the EEG findings of BFPP in three Asian patients, and confirmed that change in protein function was caused by the novel missense variant (p.Leu290Pro).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We reviewed the medical records of three siblings with BFPP including one elder girl and two identical twin boys from birth to adulthood. The clinical symptoms, electroencephalography (EEG), brain MRI, whole\u2010exome sequencing, treatment including medications, neuromodulation, and epilepsy surgery, and clinical outcomes were reviewed. The protein structure of a novel missense variant (p.Leu290Pro) was predicted by in silico studies, and molecular analysis was performed via typical flow cytometry and Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The elder girl (Patient 1) was 22\u2009years old and the twin boys (Patients 2 and 3) were 20\u2009years old at the time of publication. All of them presented with typical clinical symptoms\/signs and MRI findings of BFPP. Whole\u2010exome sequencing followed by Sanger confirmation showed that all three patients had compound heterozygous variants in the ADGRG1 gene. The missense variant (p.Leu290Pro) was confirmed to be related to a reduction in cell surface GPR56 expression. High\u2010amplitude rhythmic activity was noted in sleep EEG during infancy, which may have been due to excessive sleep spindle, and the rhythm disappeared when they were of pre\u2010school age. Partial callosotomy provided short\u2010term benefits in seizure control in Patients 1 and 2, and combined vagus nerve stimulation and partial callosotomy provided longer benefits in Patient 3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Sleep EEG findings of high\u2010amplitude rhythmic activity in our BFPP cases were only noted during infancy and childhood. We also confirmed that the missense variant (p.Leu290Pro) led to loss of function due to a reduction in cell surface GPR56 expression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12685","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T07:40:26Z","timestamp":1671176426000},"page":"154-164","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification and clinical characteristics of a novel missense <scp>ADGRG1<\/scp> variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8406-3660","authenticated-orcid":false,"given":"Cheng\u2010Yen","family":"Kuo","sequence":"first","affiliation":[{"name":"Division of Pediatric Neurology Chang Gung Children's Hospital and Chang Gung Memorial Hospital  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4570-5712","authenticated-orcid":false,"given":"Meng\u2010Han","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Neurology Kaohsiung Chang Gung Memorial Hospital  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsi\u2010Hsien","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Medicine, Chang Gung University  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Chi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou Chang Gung University  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Indian Institute of Science Education and Research  Mohali India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Chen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou Chang Gung University  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jainn\u2010Jim","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology Chang Gung Children's Hospital and Chang Gung Memorial Hospital  Taoyuan Taiwan"},{"name":"School of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"},{"name":"Division of Pediatric Critical Care and Pediatric Neurocritical Care Center Chang Gung Children's Hospital and Chang Gung Memorial Hospital  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010Cheng","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology Chang Gung Children's Hospital and Chang Gung Memorial Hospital  Taoyuan Taiwan"},{"name":"School of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang\u2010Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology Chang Gung Children's Hospital and Chang Gung Memorial Hospital  Taoyuan Taiwan"},{"name":"School of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq078"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092780"},{"issue":"5","key":"e_1_2_11_4_1","first-page":"534","article-title":"The role of GPR56\/ADGRG1 in health and disease","volume":"44","author":"Singh AK","year":"2021","journal-title":"Biom 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