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The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic <jats:italic>PIGQ<\/jats:italic> variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)\u2010anchored proteins. Transfection of wildtype <jats:italic>PIGQ<\/jats:italic> cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of <jats:italic>PIGQ<\/jats:italic>\u2010related disease and provide the first functional evidence in human cells of defective GPI\u2010anchoring due to pathogenic variants in <jats:italic>PIGQ.<\/jats:italic><\/jats:p>","DOI":"10.1002\/jimd.12278","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T08:20:05Z","timestamp":1593246005000},"page":"1321-1332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Early infantile epileptic encephalopathy due to biallelic pathogenic variants in <scp><i>PIGQ<\/i><\/scp>: Report of seven new subjects and review of the literature"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1952-5355","authenticated-orcid":false,"given":"Devon L.","family":"Johnstone","sequence":"first","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9572-118X","authenticated-orcid":false,"given":"Thi Tuyet Mai","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Research Center, CHU Sainte Justine University of Montreal  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Zambonin","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute  Ottawa Ontario Canada"},{"name":"Department of Genetics Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin D.","family":"Kernohan","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute  Ottawa Ontario Canada"},{"name":"Division of Metabolics and Newborn Screening, Department of Pediatrics Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anik","family":"St\u2010Denis","sequence":"additional","affiliation":[{"name":"Research Center, CHU Sainte Justine University of Montreal  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nissan V.","family":"Baratang","sequence":"additional","affiliation":[{"name":"Research Center, CHU Sainte Justine University of Montreal  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taila","family":"Hartley","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Geraghty","sequence":"additional","affiliation":[{"name":"Division of Metabolics and Newborn Screening, Department of Pediatrics Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Richer","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Majewski","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University  Montreal Quebec Canada"},{"name":"McGill University and Genome Quebec Innovation Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Bareke","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University  Montreal Quebec Canada"},{"name":"McGill University and Genome Quebec Innovation Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2941-7603","authenticated-orcid":false,"given":"Andrea","family":"Guerin","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Pendziwiat","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics Christian\u2010Albrechts\u2010University of Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren D. M.","family":"Pena","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8053-5918","authenticated-orcid":false,"given":"Hilde M. 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