{"doi":"10.1111/epi.17939","title":"Clinical and molecular characterization of patients with <scp><i>YWHAG</i></scp>‐related epilepsy","abstract":"OBJECTIVE: YWHAG variant alleles have been associated with a rare disease trait whose clinical synopsis includes an early onset epileptic encephalopathy with predominantly myoclonic seizures, developmental delay/intellectual disability, and facial dysmorphisms. Through description of a large cohort, which doubles the number of reported patients, we further delineate the spectrum of YWHAG-related epilepsy. METHODS: We included in this study 24 patients, 21 new and three previously described, with pathogenic/likely pathogenic variants in YWHAG. We extended the analysis of clinical, electroencephalographic, brain magnetic resonance imaging, and molecular genetic information to 24 previously published patients. RESULTS: The phenotypic spectrum of YWHAG-related disorders ranges from mild developmental delay to developmental and epileptic encephalopathy (DEE). Epilepsy onset is in the first 2 years of life. Seizure freedom can be achieved in half of the patients (13/24, 54%). Intellectual disability (23/24, 96%), behavioral disorders (18/24, 75%), neurological signs (13/24, 54%), and dysmorphisms (6/24, 25%) are common. A genotype-phenotype correlation emerged, as DEE is more represented in patients with missense variants located in the ligand-binding domain than in those with truncating or missense variants in other domains (90% vs. 19%, p < .001). SIGNIFICANCE: This study suggests that pathogenic YWHAG variants cause a wide range of clinical presentations with variable severity, ranging from mild developmental delay to DEE. In this allelic series, a genotype-phenotype correlation begins to emerge, potentially providing prognostic information for clinical management and genetic counseling.","journal":"Epilepsia","year":2024,"id":436359,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":466061,"name":"Tiziana Pisano","orcid":"0000-0001-8920-9078","position":1,"is_corresponding":false},{"id":323128,"name":"Gaëtan Lesca","orcid":"0000-0001-7691-9492","position":2,"is_corresponding":false},{"id":488202,"name":"Dana Marafi","orcid":"0000-0003-2233-3423","position":3,"is_corresponding":false},{"id":516394,"name":"Laura Licchetta","orcid":"0000-0001-7979-9895","position":4,"is_corresponding":false},{"id":733480,"name":"Florence Riccardi","orcid":"0000-0002-7223-2172","position":5,"is_corresponding":false},{"id":855138,"name":"Davide Mei","orcid":"0000-0001-6790-6251","position":6,"is_corresponding":false},{"id":1244792,"name":"Hon-Yin Brian Chung","orcid":null,"position":7,"is_corresponding":false},{"id":323114,"name":"Allan Bayat","orcid":"0000-0003-4986-8006","position":8,"is_corresponding":false},{"id":351641,"name":"Meena Balasubramanian","orcid":"0000-0003-1488-3695","position":9,"is_corresponding":false},{"id":297272,"name":"Daniel H. Lowenstein","orcid":"0000-0002-9546-2085","position":10,"is_corresponding":false},{"id":324669,"name":"Milda Endzinienė","orcid":null,"position":11,"is_corresponding":false},{"id":1244429,"name":"Maha Alotaibi","orcid":"0000-0002-2083-4489","position":12,"is_corresponding":false},{"id":1244430,"name":"Nathalie Villeneuve","orcid":"0000-0003-1584-8314","position":13,"is_corresponding":false},{"id":656920,"name":"Julia Jacobs","orcid":"0000-0003-1164-4699","position":14,"is_corresponding":false},{"id":242573,"name":"Bertrand Isidor","orcid":"0000-0001-6480-126X","position":15,"is_corresponding":false},{"id":1244431,"name":"Roberta Solazzi","orcid":"0000-0001-6657-3328","position":16,"is_corresponding":false},{"id":694088,"name":"Nicolette S. den Hollander","orcid":"0000-0002-5915-7972","position":17,"is_corresponding":false},{"id":844299,"name":"Dragan Marjanović","orcid":"0000-0001-9967-7828","position":18,"is_corresponding":false},{"id":1244793,"name":"Christelle Rougeot‐Jung","orcid":null,"position":19,"is_corresponding":false},{"id":1244432,"name":"Julien Jung","orcid":"0000-0002-9274-0086","position":20,"is_corresponding":false},{"id":1244433,"name":"Marion Lesieur‐Sebellin","orcid":"0000-0001-5046-0150","position":21,"is_corresponding":false},{"id":465610,"name":"Andrea Accogli","orcid":"0000-0001-8724-6721","position":22,"is_corresponding":false},{"id":457104,"name":"Vincenzo Salpietro","orcid":"0000-0003-0132-7921","position":23,"is_corresponding":false},{"id":747999,"name":"Nebal Waill Saadi","orcid":"0000-0001-7523-6833","position":24,"is_corresponding":false},{"id":844296,"name":"Eleni Panagiotakaki","orcid":"0000-0003-2611-0227","position":25,"is_corresponding":false},{"id":1244434,"name":"Thomas Foiadelli","orcid":"0000-0003-0961-428X","position":26,"is_corresponding":false},{"id":558895,"name":"Sylvia Redon","orcid":"0000-0001-7310-1142","position":27,"is_corresponding":false},{"id":475369,"name":"Meng‐Han Tsai","orcid":"0000-0002-4570-5712","position":28,"is_corresponding":false},{"id":694855,"name":"Francesca Bisulli","orcid":"0000-0002-1109-7296","position":29,"is_corresponding":false},{"id":325735,"name":"Trine Bjørg Hammer","orcid":"0000-0001-8935-5761","position":30,"is_corresponding":false},{"id":36511,"name":"James R. 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