{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:06:35Z","timestamp":1788941195921,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>PIGM<\/jats:italic>\n                      encodes a critical enzyme in the glycosylphosphatidylinositol (GPI)\u2010anchor biosynthesis pathway. While promoter\u2010region mutations in\n                      <jats:italic>PIGM<\/jats:italic>\n                      have been associated with a relatively mild phenotype characterized by portal vein thrombosis and absence seizures, recent evidence suggests that coding\u2010region mutations result in a more severe multisystemic disorder.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole\u2010exome sequencing reanalysis was performed in a patient with early\u2010onset developmental and epileptic encephalopathy, and subsequent matchmaking identified another patient with a similar phenotype. The pathogenicity of the variant was evaluated through multiple functional assays. To further delineate the genotypic and phenotypic spectrum of PIGM, we reviewed all patients reported to date with\n                      <jats:italic>PIGM<\/jats:italic>\n                      variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We describe two unrelated patients, both carrying the same homozygous missense variant in\n                      <jats:italic>PIGM<\/jats:italic>\n                      (c.1001A\u2009&gt;\u2009C, p.Gln334Pro), presenting with early\u2010onset developmental and epileptic encephalopathy, profound neurodevelopmental impairment, multi\u2010organ involvement, and distinctive neuroimaging findings including hypomyelination. Both patients died in infancy due to super\u2010refractory status epilepticus. Treatment with sodium phenylbutyrate was attempted in one patient without clinical benefit. Flow cytometry revealed partial GPI\u2010anchor deficiency. Comparative analysis with previously reported cases highlights a potential genotype\u2013phenotype correlation between coding region variants and disease severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Our findings establish\n                      <jats:italic>PIGM<\/jats:italic>\n                      as a causative gene of early\u2010onset developmental and epileptic encephalopathy and expand the clinical and radiological spectrum of\n                      <jats:italic>PIGM<\/jats:italic>\n                      deficiency to include hypomyelination and prenatal onset. This study underscores the importance of including\n                      <jats:italic>PIGM<\/jats:italic>\n                      in the differential diagnosis of developmental and epileptic encephalopathy and leukoencephalopathies and provides further insight into the molecular mechanisms underlying phenotypic variability of GPI\u2010anchor disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70341","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:48:52Z","timestamp":1772970532000},"page":"1759-1771","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Developmental and Epileptic Encephalopathy due to Biallelic Pathogenic Variants in\n                    <scp>\n                      <i>PIGM<\/i>\n                    <\/scp>"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5116-6316","authenticated-orcid":false,"given":"J\u00falia","family":"Sala\u2010Coromina","sequence":"first","affiliation":[{"name":"Departament de Pediatria, Obstetr\u00edcia i Ginecologia i de Medicina Preventiva i Salut P\u00fablica Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Vall D'hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5762-4023","authenticated-orcid":false,"given":"Anna","family":"Marc\u00e9\u2010Grau","sequence":"additional","affiliation":[{"name":"Vall D'hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Masotto","sequence":"additional","affiliation":[{"name":"Vall D'hebron Research Institute  Barcelona Spain"},{"name":"Department of Genetics Vall D'hebron University Hospital  Barcelona 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Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7340-2161","authenticated-orcid":false,"given":"M\u00f3nica","family":"Martinez\u2010Gallo","sequence":"additional","affiliation":[{"name":"Vall D'hebron Research Institute  Barcelona Spain"},{"name":"Department of Immunology Vall D'hebron University Hospital  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Colobran","sequence":"additional","affiliation":[{"name":"Vall D'hebron Research Institute  Barcelona Spain"},{"name":"Department of Immunology Vall D'hebron University Hospital  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Sanchez\u2010Monta\u00f1ez","sequence":"additional","affiliation":[{"name":"Section of Neuroradiology, Department of Pediatric Radiology Vall D'hebron University Hospital  Barcelona 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