Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings
Abstract Objective Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic‐related migration disorder. It has been attributed to loss‐of‐function of the ADGRG1 gene, which encodes an adhesion G protein‐coupled receptor, ADGRG1/GPR56. We report the EEG findings of BFPP in three Asian patient...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-03-01
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| Series: | Epilepsia Open |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/epi4.12685 |
| _version_ | 1827996868194336768 |
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| author | Cheng‐Yen Kuo Meng‐Han Tsai Hsi‐Hsien Lin Yu‐Chi Wang Abhishek Kumar Singh Chih‐Chen Chang Jainn‐Jim Lin Po‐Cheng Hung Kuang‐Lin Lin |
| author_facet | Cheng‐Yen Kuo Meng‐Han Tsai Hsi‐Hsien Lin Yu‐Chi Wang Abhishek Kumar Singh Chih‐Chen Chang Jainn‐Jim Lin Po‐Cheng Hung Kuang‐Lin Lin |
| author_sort | Cheng‐Yen Kuo |
| collection | DOAJ |
| description | Abstract Objective Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic‐related migration disorder. It has been attributed to loss‐of‐function of the ADGRG1 gene, which encodes an adhesion G protein‐coupled 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). Methods 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‐exome 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. Results The elder girl (Patient 1) was 22 years old and the twin boys (Patients 2 and 3) were 20 years old at the time of publication. All of them presented with typical clinical symptoms/signs and MRI findings of BFPP. Whole‐exome 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‐amplitude 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‐school age. Partial callosotomy provided short‐term benefits in seizure control in Patients 1 and 2, and combined vagus nerve stimulation and partial callosotomy provided longer benefits in Patient 3. Significance Sleep EEG findings of high‐amplitude 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. |
| first_indexed | 2024-04-10T05:19:13Z |
| format | Article |
| id | doaj.art-7f008ba501fa4367a2be4dc7963049e4 |
| institution | Directory Open Access Journal |
| issn | 2470-9239 |
| language | English |
| last_indexed | 2024-04-10T05:19:13Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj.art-7f008ba501fa4367a2be4dc7963049e42023-03-08T12:35:53ZengWileyEpilepsia Open2470-92392023-03-018115416410.1002/epi4.12685Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblingsCheng‐Yen Kuo0Meng‐Han Tsai1Hsi‐Hsien Lin2Yu‐Chi Wang3Abhishek Kumar Singh4Chih‐Chen Chang5Jainn‐Jim Lin6Po‐Cheng Hung7Kuang‐Lin Lin8Division of Pediatric Neurology Chang Gung Children's Hospital and Chang Gung Memorial Hospital Taoyuan TaiwanSchool of Medicine, College of Medicine Chang Gung University Taoyuan TaiwanDepartment of Microbiology and Immunology College of Medicine, Chang Gung University Taoyuan TaiwanDepartment of Neurosurgery, Chang Gung Memorial Hospital at Linkou Chang Gung University Taoyuan TaiwanDepartment of Biological Sciences Indian Institute of Science Education and Research Mohali IndiaDepartment of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou Chang Gung University Taoyuan TaiwanDivision of Pediatric Neurology Chang Gung Children's Hospital and Chang Gung Memorial Hospital Taoyuan TaiwanDivision of Pediatric Neurology Chang Gung Children's Hospital and Chang Gung Memorial Hospital Taoyuan TaiwanDivision of Pediatric Neurology Chang Gung Children's Hospital and Chang Gung Memorial Hospital Taoyuan TaiwanAbstract Objective Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic‐related migration disorder. It has been attributed to loss‐of‐function of the ADGRG1 gene, which encodes an adhesion G protein‐coupled 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). Methods 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‐exome 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. Results The elder girl (Patient 1) was 22 years old and the twin boys (Patients 2 and 3) were 20 years old at the time of publication. All of them presented with typical clinical symptoms/signs and MRI findings of BFPP. Whole‐exome 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‐amplitude 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‐school age. Partial callosotomy provided short‐term benefits in seizure control in Patients 1 and 2, and combined vagus nerve stimulation and partial callosotomy provided longer benefits in Patient 3. Significance Sleep EEG findings of high‐amplitude 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.https://doi.org/10.1002/epi4.12685congenital CNS malformationepilepsygeneticpolymicrogyria |
| spellingShingle | Cheng‐Yen Kuo Meng‐Han Tsai Hsi‐Hsien Lin Yu‐Chi Wang Abhishek Kumar Singh Chih‐Chen Chang Jainn‐Jim Lin Po‐Cheng Hung Kuang‐Lin Lin Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings Epilepsia Open congenital CNS malformation epilepsy genetic polymicrogyria |
| title | Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings |
| title_full | Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings |
| title_fullStr | Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings |
| title_full_unstemmed | Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings |
| title_short | Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings |
| title_sort | identification and clinical characteristics of a novel missense adgrg1 variant in bilateral frontoparietal polymicrogyria the electroclinical change from infancy to adulthood after callosotomy in three siblings |
| topic | congenital CNS malformation epilepsy genetic polymicrogyria |
| url | https://doi.org/10.1002/epi4.12685 |
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