{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:55:16Z","timestamp":1774439716573,"version":"3.50.1"},"reference-count":66,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A rare autosomal recessive disorder known as hyperphosphatasia with impaired intellectual development syndrome (HPMRS), also referred to as Mabry syndrome, is caused by a deficiency in glycosylphosphatidylinositol (GPI). Elevated blood alkaline phosphatase (ALP) levels, cognitive impairment, and epileptic seizures are among its key features. These pathways are involved in the synthesis of GPI and the transfer of GPI anchor to the proteins, fatty acid remodeling, and transport of GPI\u2010anchored proteins (GPI\u2010APs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using exome sequencing (ES), the cause of hyperphosphatasia and ID of an 11\u2010year\u2010old girl from non\u2010consanguineous parents was solved, and the results confirmed by direct Sanger sequencing method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ES identified a novel homozygous pathogenic variant,\n                      <jats:italic>PGAP3<\/jats:italic>\n                      (NM_033419.5: c.202dupT, p.Cys68fs*2) that segregated within the family members. To the best of our knowledge at the time of writing this manuscript, this variant has not been reported in HPMRS in the literature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that the p.Cys68fs*2 variant may disrupt normal protein function and likely disrupt its interaction with its associated partner proteins, potentially leading to disruption of GPI biosynthesis. We present a novel pathogenic variant thus expanding the phenotypic and mutational spectrum of this extremely rare disorder. Elevated ALP assays and ES are valuable diagnostic tools for HPMRS. Additionally, a comprehensive literature review was conducted to expand the phenotypic and genotypic spectrum within the\n                      <jats:italic>PGAP3<\/jats:italic>\n                      gene responsible for HPMRS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70206","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T04:24:54Z","timestamp":1774239894000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reporting a Novel Disease Causing Variant in\n                    <i>PGAP3<\/i>\n                    Associated With Hyperphosphatasia and Intellectual Disability: A Case Report and Comprehensive Literature Review"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-3915","authenticated-orcid":false,"given":"Arash","family":"Salmaninejad","sequence":"first","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Medical Genetics, Baran Laboratory  Rasht Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6151-7826","authenticated-orcid":false,"given":"Mohammad Reza","family":"Seyedtaghia","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Hormozgan University of Medical Sciences  Bandar Abbas Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1602-3605","authenticated-orcid":false,"given":"Ali Hosseini","family":"Bereshneh","sequence":"additional","affiliation":[{"name":"Children's Hospital Medical Center Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1110-4560","authenticated-orcid":false,"given":"Nasrin","family":"Azizi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Baran Laboratory  Rasht Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8956-5205","authenticated-orcid":false,"given":"Reza","family":"Bayat","sequence":"additional","affiliation":[{"name":"Pediatric Diseases Research Center Guilan University of Medical Sciences  Rasht Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6361-0151","authenticated-orcid":false,"given":"Somaye","family":"Esnaashari","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Baran Laboratory  Rasht Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7612-8604","authenticated-orcid":false,"given":"Vahid","family":"Aminzadeh","sequence":"additional","affiliation":[{"name":"Pediatric Diseases Research Center Guilan University of Medical Sciences  Rasht Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-3044","authenticated-orcid":false,"given":"Shahin","family":"Koohmanaee","sequence":"additional","affiliation":[{"name":"Pediatric Diseases Research Center Guilan University of Medical Sciences  Rasht Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0591-5205","authenticated-orcid":false,"given":"Shahram","family":"Savad","sequence":"additional","affiliation":[{"name":"Genome\u2010Nilou Laboratory  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8742-2844","authenticated-orcid":false,"given":"Majid","family":"Mojarrad","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4976-1404","authenticated-orcid":false,"given":"Setila","family":"Dalili","sequence":"additional","affiliation":[{"name":"Pediatric Diseases Research Center Guilan University of Medical Sciences  Rasht Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,22]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13033"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-019-0902-5"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.37"},{"issue":"9","key":"e_1_2_14_5_1","article-title":"A Novel PGAP3 Gene Mutation\u2010Related Megalocornea Can Be Misdiagnosed as Primary Congenital Glaucoma","volume":"14","author":"Alhaidari A. I.","year":"2022","journal-title":"Cureus"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2023.107688"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40627"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.15142"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020453"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61797"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.11.009"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2022.04.003"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158725"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2020.01.006"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-102156"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081782"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-017-7197-9_7"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.09.002"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbot.2018.00023"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-019-1440-8"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.03.008"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37950"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2019.103802"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34102"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2010.01.002"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.241"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.12.012"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv331"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9299-3"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2016.01.007"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.08.070"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.90.130"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23006"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.004"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.03.011"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.653"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a8411a"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(70)80047-6"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-10-0885"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e3280147130"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.087114"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_14_45_1","volume-title":"Discovering the Brain","author":"Medicine, I. o. and N. A. o. Sciences","year":"1992"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12347"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0654-9"},{"key":"e_1_2_14_48_1","doi-asserted-by":"crossref","unstructured":"Mukai T. S.Kato H.Tanaka et\u00a0al.2024. \u201cA Case of Inherited Glycosylphosphatidylinositol Deficiency Caused by PGAP3 Variant With Uniparental Isodisomy on Chromosome 17.\u201d12 no.7:e2452.","DOI":"10.1002\/mgg3.2452"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12508"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1599148"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2016.10.027"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9752-1"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.32"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2024.1419976"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231921"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6150-6-37"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3470234"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/hgv.2018.5"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2005.08.020"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35202"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.146"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03087-z"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12060"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2016.04.008"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1575-0"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-017-0109-y"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70206","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.70206","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70206","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T08:35:30Z","timestamp":1774427730000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":66,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/mgg3.70206"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70206","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-05-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70206"}}