{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:06:18Z","timestamp":1790766378677,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"abstract":"\n Objective<\/jats:title>\n \n Glycosylphosphatidylinositol (\n GPI<\/jats:styled-content>\n )\u2010anchored proteins play critical roles in nervous system function. Pathogenic variants in genes involved in\n GPI<\/jats:styled-content>\n \u2010anchor biosynthesis cause early\u2010onset multisystem disorders known as inherited\n GPI<\/jats:styled-content>\n deficiencies. We describe a novel neuromuscular phenotype associated with\n PIGB<\/jats:styled-content>\n deficiency.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Patients with neuromuscular disease carrying\n \n PIGB<\/jats:italic>\n <\/jats:styled-content>\n variants were identified, and clinical data collected.\n GPI<\/jats:styled-content>\n \u2010anchored protein and free\u2010\n GPI<\/jats:styled-content>\n expression were assessed by flow cytometry and variants validated in a\n \n PIGB<\/jats:italic>\n <\/jats:styled-content>\n knockout cellular model.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Biallelic\n \n PIGB<\/jats:italic>\n <\/jats:styled-content>\n variants were identified in 12 patients (median age 32\u2009years, range 15\u201352\u2009years) from 9 independent families. Of 15 variants, 13 were novel, including a de novo inversion generating a\n \n PIGB<\/jats:italic>\n <\/jats:styled-content>\n ::\n \n RAB27A<\/jats:italic>\n <\/jats:styled-content>\n gene fusion. Of 12 patients, 10 presented with distal lower\u2010limb weakness, and neurophysiological studies demonstrated a motor\u2010predominant neuropathy with frequent conduction blocks in all patients. Signs of nerve hyperexcitability were observed in 9 patients, with electromyography neuromyotonic discharges and myokymia compatible with peripheral nerve hyperexcitability in 6. A total of 3 patients showed a decremental response on repetitive nerve stimulation; 2 were symptomatic and responded to pyridostigmine, consistent with neuromuscular junction transmission defect. Neurodevelopmental features were inconsistent. Flow cytometry revealed variable reductions of\n GPI<\/jats:styled-content>\n \u2010anchored proteins, but consistent reduction of free\n GPI<\/jats:styled-content>\n in blood cells. Novel variants impaired\n GPI<\/jats:styled-content>\n \u2010anchor expression in vitro.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n \n We expand the phenotypic spectrum of inherited\n GPI<\/jats:styled-content>\n deficiencies with a novel neuromuscular syndrome encompassing motor neuropathy with conduction blocks, peripheral nerve hyperexcitability, and occasional neuromuscular junction defects associated with\n \n PIGB<\/jats:italic>\n <\/jats:styled-content>\n variants.\n \n PIGB<\/jats:italic>\n <\/jats:styled-content>\n and other\n GPI<\/jats:styled-content>\n \u2010anchor biosynthesis genes should be considered in motor neuropathy with conduction blocks. ANN NEUROL 2026\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ana.78358","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:50:12Z","timestamp":1790765412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic\n \n PIGB<\/i>\n <\/scp>\n Variants Cause Motor Neuropathy with Conduction Blocks and Peripheral Nerve Hyperexcitability"],"prefix":"10.1002","author":[{"given":"Gorka","family":"Fern\u00e1ndez\u2010Eulate","sequence":"first","affiliation":[{"name":"Nord\/Est\/Ile\u2010de\u2010France Neuromuscular Diseases Reference Center, Neuromyology service, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, AP\u2010HP Sorbonne Universit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5785-0685","authenticated-orcid":false,"given":"Romain","family":"Duval","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 des Antilles, INSERM, EFS, BIGR U1134, Laboratory of Blood Group Antigens, Hematopoiesis, and Sickle Cell Disease Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Konyukh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Henri Mondor Hospital, AP\u2010HP Cr\u00e9teil France"},{"name":"Laboratoire de biologie m\u00e9dicale multisites SeqOIA \u2013 PFMG2025 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Bertini","sequence":"additional","affiliation":[{"name":"Unit of Rare Neurological Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta Milan 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Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5183-780X","authenticated-orcid":false,"given":"Theresa","family":"Brunet","sequence":"additional","affiliation":[{"name":"Technical University of Munich, TUM School of Medicine and Health, Institute of Human Genetics, TUM University Hospital Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"M\u00fcller\u2010Felber","sequence":"additional","affiliation":[{"name":"LMU Munich University Hospital, Hauner Children's Hospital, Pediatric Neurology and Developmental Medicine Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8711-5526","authenticated-orcid":false,"given":"Helena F.","family":"Pernice","sequence":"additional","affiliation":[{"name":"Department of Neurology and Experimental Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin 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