{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T06:02:43Z","timestamp":1780120963845,"version":"3.54.0"},"reference-count":12,"publisher":"IMR Press","issue":"5","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Liuzhou Science and Technology Bureau","award":["2022CAC0104"],"award-info":[{"award-number":["2022CAC0104"]}]},{"name":"High-Level Talents Fund of Liuzhou People's Hospital affiliated to Guangxi Medical University","award":["LRYGCC202205"],"award-info":[{"award-number":["LRYGCC202205"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Neurol."],"abstract":"<jats:p>Introduction: Developmental and epileptic encephalopathy (DEE) is a group of severe neurological disorders characterized by early-onset epilepsy and developmental delay, often caused by genetic variants. Cdc42 Guanine Nucleotide Exchange Factor 9 (ARHGEF9) gene variants have been linked to DEE, yet novel variants and their phenotypic presentations remain incompletely characterized. Clinical Cases: Herein, we describe two siblings with DEE caused by a novel deletion variant in the ARHGEF9 gene. Both patients presented with early-onset epilepsy and developmental delay. Whole-exome sequencing identified a hemizygous c.1037_1045del variant in the ARHGEF9 gene (NM_015185.2) in both brothers, which is reported here for the first time. Notably, the two siblings exhibited a marked difference in outcomes: the elder brother achieved good seizure control with anti-epileptic drugs, while the proband, despite multidrug therapy and vagus nerve stimulation (VNS), exhibited a limited response and continued to experience frequent seizures. Conclusions: These cases expand the genotypic spectrum of ARHGEF9-related disorders and underscore the intrafamilial phenotypic variability associated with this gene. These findings emphasize the significance of early genetic testing for establishing a diagnosis, assessing prognosis, and facilitating genetic counseling.<\/jats:p>","DOI":"10.31083\/rn46598","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T05:34:23Z","timestamp":1780119263000},"source":"Crossref","is-referenced-by-count":0,"title":["Developmental and Epileptic Encephalopathy Due to a Novel ARHGEF9 Deletion Variant: Case Series of Two Siblings"],"prefix":"10.31083","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7501-2503","authenticated-orcid":true,"given":"Jie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou Key Laboratory of Epilepsy Prevention and Research, 545000 Liuzhou, Guangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8160-5336","authenticated-orcid":true,"given":"Guangshun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou Key Laboratory of Epilepsy Prevention and Research, 545000 Liuzhou, Guangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9722-0890","authenticated-orcid":true,"given":"Yizhi","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou Key Laboratory of Epilepsy Prevention and Research, 545000 Liuzhou, Guangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017; 58: 512\u2013521.","DOI":"10.1111\/epi.13709"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Shimojima K, Sugawara M, Shichiji M, Mukaida S, Takayama R, Imai K, et al. Loss-of-function mutation of collybistin is responsible for X-linked mental retardation associated with epilepsy. Journal of Human Genetics. 2011; 56: 561\u2013565.","DOI":"10.1038\/jhg.2011.58"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Lesca G, Till M, Labalme A, Vallee D, Hugonenq C, Philip N, et al. De novo Xq11.11 microdeletion including ARHGEF9 in a boy with mental retardation, epilepsy, macrosomia, and dysmorphic features. American Journal of Medical Genetics. Part A. 2011; 155A: 1706\u20131711.","DOI":"10.1002\/ajmg.a.34004"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Freri E, Castellotti B, Didato G, DiFrancesco JC, Granata T. 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The Journal of International Medical Research. 2021; 49: 3000605211058372.","DOI":"10.1177\/03000605211058372"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022; 63: 1398\u20131442.","DOI":"10.1111\/epi.17241"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Scala M, Zonneveld-Huijssoon E, Brienza M, Mecarelli O, van der Hout AH, Zambrelli E, et al. De novo ARHGEF9 missense variants associated with neurodevelopmental disorder in females: expanding the genotypic and phenotypic spectrum of ARHGEF9 disease in females. Neurogenetics. 2021; 22: 87\u201394.","DOI":"10.1007\/s10048-020-00622-5"}],"container-title":["Revista de Neurolog\u00eda"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/RN\/81\/5\/10.31083\/RN46598","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T05:34:28Z","timestamp":1780119268000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/RN\/81\/5\/10.31083\/RN46598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026]]}},"alternative-id":["S0210-0010(26)02924-0"],"URL":"https:\/\/doi.org\/10.31083\/rn46598","relation":{},"ISSN":["0210-0010","1576-6578"],"issn-type":[{"value":"0210-0010","type":"print"},{"value":"1576-6578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]},"article-number":"46598"}}