{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:47:51Z","timestamp":1791920871676,"version":"4.3.4"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T00:00:00Z","timestamp":1726876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pediatric intestinal pseudo\u2010obstruction (PIPO) is a rare congenital disorder of the enteric nervous system with distal colon aganglionosis potentially leading to intestinal obstruction. Recently, biallelic variants in\n                    <jats:italic>KIF26A<\/jats:italic>\n                    , encoding a crucial motor protein for the migration and differentiation of enteric neural crest cells, have been associated with a neurodevelopmental condition featuring cortical defects and PIPO\u2010like features, though in absence of aganglionosis. So far, only 10 patients have been reported. In this study, we investigated three subjects with congenital hydrocephalus, neurodevelopmental impairment, and intestinal obstruction megacolon syndrome. Brain MRI revealed malformations within cortical dysplasia spectrum, including polymicrogyria and heterotopia. Pathology study of the intestine revealed aganglionosis and elevated acetylcholinesterase activity in parasympathetic nerve fibers. Through trio\u2010exome sequencing (ES), we detected four novel biallelic\n                    <jats:italic>KIF26A<\/jats:italic>\n                    variants, including two missense changes (#1) and two distinct homozygous truncating variants in (#2 and #3). All variants are rare and predicted to be deleterious according to in silico tools. To characterize the impact of the missense variants, we performed 3D protein modeling using Alphafold3 and YASARA. Mutants exhibited increased energy scores compared to wild\u2010type protein, supporting a significant structural destabilization of the protein. Our study expands the genotype and phenotype spectrum of the emerging\n                    <jats:italic>KIF26A<\/jats:italic>\n                    \u2010related disorder.\n                  <\/jats:p>","DOI":"10.1111\/cge.14621","type":"journal-article","created":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T03:34:38Z","timestamp":1726889678000},"page":"83-90","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel\n                    <i>KIF26A<\/i>\n                    variants associated with pediatric intestinal pseudo\u2010obstruction (\n                    <scp>PIPO<\/scp>\n                    ) and brain developmental defects"],"prefix":"10.1111","volume":"107","author":[{"given":"Mohammad Sadegh Shams","family":"Nosrati","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"U.O.C. Genetica Medica IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Doustmohammadi","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biophysics, Faculty of Biology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariasavina","family":"Severino","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruccio","family":"Romano","sequence":"additional","affiliation":[{"name":"Genomics and Clinical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9906-1556","authenticated-orcid":false,"given":"Mahdi","family":"Zafari","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Hesam","family":"Nemati","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Pasteur Institute of Iran  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Velmans","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Netzer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Breuer","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Faculty of Medicine and University Hospital Cologne University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse Julia","family":"Broekaert","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Faculty of Medicine and University Hospital Cologne University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6724-0015","authenticated-orcid":false,"given":"Alexander","family":"Joachim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Health Helios University Medical Center Wuppertal, Witten\/Herdecke University  Witten Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihad","family":"Almasri","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences College of Health Sciences Qatar University  Doha Qatar"},{"name":"Department of Physiotherapy School of Rehabilitation Sciences University of Jordan  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Kruer","sequence":"additional","affiliation":[{"name":"Pediatric Movement Disorders Program, Division of Pediatric Neurology Barrow Neurological Institute, Phoenix Children's Hospital  Phoenix Arizona USA"},{"name":"Departments of Child Health, Neurology, and Cellular &amp; Molecular Medicine, and Program in Genetics University of Arizona College of Medicine\u2013Phoenix  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1051-5051","authenticated-orcid":false,"given":"Peter","family":"Skidmore","sequence":"additional","affiliation":[{"name":"Pediatric Movement Disorders Program, Division of Pediatric Neurology Barrow Neurological Institute, Phoenix Children's Hospital  Phoenix Arizona USA"},{"name":"Departments of Child Health, Neurology, and Cellular &amp; Molecular Medicine, and Program in Genetics University of Arizona College of Medicine\u2013Phoenix  Phoenix Arizona USA"},{"name":"College of Health Solutions Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2677-9847","authenticated-orcid":false,"given":"Pritha","family":"Bisarad","sequence":"additional","affiliation":[{"name":"Pediatric Movement Disorders Program, Division of Pediatric Neurology Barrow Neurological Institute, Phoenix Children's Hospital  Phoenix Arizona USA"},{"name":"Departments of Child Health, Neurology, and Cellular &amp; Molecular Medicine, and Program in Genetics University of Arizona College of Medicine\u2013Phoenix  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumana","family":"Hoque","sequence":"additional","affiliation":[{"name":"Pediatric Movement Disorders Program, Division of Pediatric Neurology Barrow Neurological Institute, Phoenix Children's Hospital  Phoenix Arizona USA"},{"name":"Departments of Child Health, Neurology, and Cellular &amp; Molecular Medicine, and Program in Genetics University of Arizona College of Medicine\u2013Phoenix  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somayeh","family":"Bakhtiari","sequence":"additional","affiliation":[{"name":"Pediatric Movement Disorders Program, Division of Pediatric Neurology Barrow Neurological Institute, Phoenix Children's Hospital  Phoenix Arizona USA"},{"name":"Departments of Child Health, Neurology, and Cellular &amp; Molecular Medicine, and Program in Genetics University of Arizona College of Medicine\u2013Phoenix  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalaura","family":"Torella","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine University of Campania \"Luigi Vanvitelli\"  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Nigro","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine University of Campania \"Luigi Vanvitelli\"  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Buffelli","sequence":"additional","affiliation":[{"name":"Fetal\u2010Perinatal Pathology Unit IRCCS\u2010Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezio","family":"Fulcheri","sequence":"additional","affiliation":[{"name":"Fetal\u2010Perinatal Pathology Unit IRCCS\u2010Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Pediatric Pathology University Clinic of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"U.O.C. Genetica Medica IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Capra","sequence":"additional","affiliation":[{"name":"Genomics and Clinical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-7239","authenticated-orcid":false,"given":"Marcello","family":"Scala","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"U.O.C. Genetica Medica IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001982"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.638093"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2022-108483"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.10.023"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-022-02513-1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.09.011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38593"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac106"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200650"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.3.325"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3367"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.1.16010"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006908200"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.18.11378"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.075"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2005.07.006"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.2.954"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13064-017-0082-5"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10123395"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112744"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14621","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T21:55:07Z","timestamp":1734040507000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,21]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/cge.14621"],"URL":"https:\/\/doi.org\/10.1111\/cge.14621","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14621\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14621\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14621\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14621\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14621\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14621\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,21]]},"assertion":[{"value":"2024-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}