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This study reports a 41-year-old woman with tics, myoclonus, language difficulties, gait instability, tremor, absence seizures, and psychotic symptoms with hallucinations and misidentification. Specialists performed MRI, video-EEG, and FDG-PET/MRI, followed by whole exome sequencing and ACMG-guided variant interpretation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/expanding-the-spectrum-of-nus1-related-progressive-myoclonic-epilepsy-a-novel-variant-and-exploratory-use-of-metformin/408598/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/expanding-the-spectrum-of-nus1-related-progressive-myoclonic-epilepsy-a-novel-variant-and-exploratory-use-of-metformin/408598.png","ImageObject",300,407,{"name":92,"@type":93},"ahduag","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What clinical features are reported in the NUS1-related case?","Question",{"text":112,"@type":113},"The patient developed tics, myoclonus, language difficulties, gait instability, tremor, absence seizures, and psychotic symptoms including persistent hallucinations and delusional misidentification.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the genetic variant identified and interpreted?",{"text":117,"@type":113},"Neurology and psychiatry reviewed clinical data; whole exome sequencing guided by HPO terms was performed, and variants were interpreted using ACMG guidelines.",{"name":119,"@type":110,"acceptedAnswer":120},"What was the identified NUS1 variant and what treatment changes were made?",{"text":121,"@type":113},"A novel heterozygous frameshift likely pathogenic variant (c. 248del, p. 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Genet. 16:1665623 .  \ndoi: 10.3389/fgene.2025.1665623  \nCOPYRIGHT  \n© 2025 Sau, López-Rodríguez, Falip, EsteveGarcia, Sala-Padró, Aguilera, Navarro-Romero, Lasa-Aranzasti, Rodríguez-Bel and HernándezPérez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nExpanding the spectrum of NUS1-related progressive myoclonic epilepsy: a novel variant and exploratory use of metformin  \nCristina Sau 1, Sergi López-Rodríguez 2, Mercè Falip 3, Anna Esteve-Garcia 1, Jacint Sala-Padró 3, Cinthia Aguilera 4, Alba Navarro-Romero 5, Amaia Lasa-Aranzasti 6,  \nLaura Rodríguez-Bel 7 and Guillermo Hernández-Pérez 3*  \n1Department of Clinical Genetics, Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain, 2Department of Psychiatry, Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain, 3Department of Neurology, Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain, 4Genetics Laboratory, Metropolitan South Clinical Laboratory, Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain, 5Neurology Area, Health in Code, Valencia, Spain, 6Department of Clinical and Molecular Genetics, Hospital Universitari Vall d’Hebron, Valld’Hebron Institut de Recerca (VHIR), Medicine Genetics Group, Barcelona, Spain, 7Nuclear Medicine Department, ICS-IDI, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain  \nIntroduction: Progressive myoclonic epilepsies (PME) are rare genetic disorders typically presenting with myoclonus, seizures, and cognitive decline. While several genes are associated with PME, the NUS1 gene has recently emerged as a potential cause. We report the case of a 41-year-old woman who presented with tics, myoclonus, and language difficulties followed by gait instability, tremor, absence seizures, and psychotic symptoms including persistent hallucinations and delusional misidentification.  \nMethods: Neurology and psychiatry specialists reviewed clinical data. Brain MRI, scalp video-EEG monitoring, and [18F]-FDG-PET/MRI were performed following standardized protocols. Whole exome sequencing (WES) guided by human phenotype ontology (HPO) terms was performed, and variants were interpreted according to American College of Medical Genetics and Genomics (ACMG) guidelines. Additionally, we conducted a review of previously reported cases of NUS1 pathogenic/likely pathogenic variants associated with PME to better characterize the clinical and paraclinical features and to explore potentia","cbCaigblhw6C8lmR","https://ap.wps.com/l/cbCaigblhw6C8lmR","pdf",3430466,15,"English","# Introduction\n# Methods\n# Results\n# Discussion","[{\"question\":\"What clinical features are reported in the NUS1-related case?\",\"answer\":\"The patient developed tics, myoclonus, language difficulties, gait instability, tremor, absence seizures, and psychotic symptoms including persistent hallucinations and delusional misidentification.\"},{\"question\":\"How was the genetic variant identified and interpreted?\",\"answer\":\"Neurology and psychiatry reviewed clinical data; whole exome sequencing guided by HPO terms was performed, and variants were interpreted using ACMG guidelines.\"},{\"question\":\"What was the identified NUS1 variant and what treatment changes were made?\",\"answer\":\"A novel heterozygous frameshift likely pathogenic variant (c. 248del, p. His83Profs*22) was found. Metformin was introduced alongside a revision of the patient’s existing psychiatric treatment.\"}]","Expanding the spectrum of NUS1-related progressive myoclonic epilepsy - a novel variant and exploratory use of metformin | PDF",1790579894,38]