{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:53:04Z","timestamp":1788335584405,"version":"build-2803163510"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007457","name":"JPB Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007457","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014370","name":"Simons Foundation Autism Research Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014370","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012317","name":"UCLH Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Phosphatidylinositol Glycan Anchor Biosynthesis class H (PIGH) is an essential player in the glycosylphosphatidylinositol (GPI) synthesis, an anchor for numerous cell membrane\u2010bound proteins. PIGH deficiency is a newly described and rare disorder associated with developmental delay, seizures and behavioral difficulties. Herein, we report three new unrelated families with two different bi\u2010allelic\n                    <jats:italic>PIGH<\/jats:italic>\n                    variants, including one new variant p.(Arg163Trp) which seems associated with a more severe phenotype. The common clinical features in all affected individuals are developmental delay\/intellectual disability and hypotonia. Variable clinical features include seizures, autism spectrum disorder, apraxia, severe language delay, dysarthria, feeding difficulties, facial dysmorphisms, microcephaly, strabismus, and musculoskeletal anomalies. The two siblings homozygous for the p.(Arg163Trp) variant have severe symptoms including profound psychomotor retardation, intractable seizures, multiple bone fractures, scoliosis, loss of independent ambulation, and delayed myelination on brain MRI. Serum iron levels were significantly elevated in one individual. All tested individuals with PIGH deficiency had normal alkaline phosphatase and CD16, a GPI\u2010anchored protein (GPI\u2010AP), was found to be decreased by 60% on granulocytes from one individual. This study expands the PIGH deficiency phenotype range toward the severe end of the spectrum with the identification of a novel pathogenic variant.\n                  <\/jats:p>","DOI":"10.1111\/cge.13877","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T06:15:46Z","timestamp":1604643346000},"page":"313-317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["PIGH deficiency can be associated with severe neurodevelopmental and skeletal manifestations"],"prefix":"10.1111","volume":"99","author":[{"given":"Camille","family":"Tremblay\u2010Lagani\u00e8re","sequence":"first","affiliation":[{"name":"Department of Pediatrics CHU Sainte\u2010Justine  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rauan","family":"Kaiyrzhanov","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery  London UK"}],"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":"Department of Pediatrics CHU Sainte\u2010Justine  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamran","family":"Salayev","sequence":"additional","affiliation":[{"name":"Department of Neurology Azerbaijan Medical University  Baku Azerbaijan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana T.","family":"Chilton","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics Columbia University Irving Medical Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics Columbia University Irving Medical Center  New York NY USA"},{"name":"Department of Medicine Columbia University Irving Medical Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Madden","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Manton Center for Orphan Disease Research, Boston Children's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanika","family":"Phornphutkul","sequence":"additional","affiliation":[{"name":"Departments of Pediatric and Pathology The Warren Alpert Medical School of Brown University  Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj B.","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Manton Center for Orphan Disease Research, Boston Children's Hospital  Boston MA USA"},{"name":"Division of Newborn Medicine Boston Children's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9713-7107","authenticated-orcid":false,"given":"Philippe M.","family":"Campeau","sequence":"additional","affiliation":[{"name":"Department of Pediatrics CHU Sainte\u2010Justine  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R063313"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13425"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.331090"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/yea.783"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23420"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23426"},{"issue":"1","key":"e_1_2_9_8_1","first-page":"D756","article-title":"UCSC genome browser enters 20th year","volume":"48","author":"Lee CM","year":"2020","journal-title":"Nucleic Acids 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