{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:49:24Z","timestamp":1782362964302,"version":"3.54.5"},"reference-count":12,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["338446"],"award-info":[{"award-number":["338446"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    HIDEA syndrome is caused by biallelic pathogenic variants in\n                    <jats:italic>P4HTM<\/jats:italic>\n                    . The phenotype is characterized by muscular and central hypotonia, hypoventilation including obstructive and central sleep apneas, intellectual disability, dysautonomia, epilepsy, eye abnormalities, and an increased tendency to develop respiratory distress during pneumonia. Here, we report six new patients with HIDEA syndrome caused by five different biallelic\n                    <jats:italic>P4HTM<\/jats:italic>\n                    variants, including three novel variants. We describe two Finnish enriched pathogenic\n                    <jats:italic>P4HTM<\/jats:italic>\n                    variants and demonstrate that these variants are embedded within founder haplotypes. We review the clinical data from all previously published patients with HIDEA and characterize all reported\n                    <jats:italic>P4HTM<\/jats:italic>\n                    pathogenic variants associated with HIDEA in silico. All known pathogenic variants in\n                    <jats:italic>P4HTM<\/jats:italic>\n                    result in either premature stop codons, an intragenic deletion, or amino acid changes that impact the active site or the overall stability of P4H\u2010TM protein. In all cases, normal P4H\u2010TM enzyme function is expected to be lost or severely decreased. This report expands knowledge of the genotypic and phenotypic spectrum of the disease.\n                  <\/jats:p>","DOI":"10.1111\/cge.14203","type":"journal-article","created":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T23:28:12Z","timestamp":1659223692000},"page":"444-450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>HIDEA<\/scp>\n                    syndrome is caused by biallelic, pathogenic, rare or founder\n                    <i>P4HTM<\/i>\n                    variants impacting the active site or the overall stability of the\n                    <scp>P4H\u2010TM<\/scp>\n                    protein"],"prefix":"10.1111","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-699X","authenticated-orcid":false,"given":"Minna","family":"Kraatari\u2010Tiri","sequence":"first","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Department of Clinical Genetics and Medical Research Center Oulu University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-5921","authenticated-orcid":false,"given":"Leila","family":"Soikkonen","sequence":"additional","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Department of Clinical Genetics and Medical Research Center Oulu University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6641-5856","authenticated-orcid":false,"given":"Matti","family":"Myllykoski","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0151-6482","authenticated-orcid":false,"given":"Yalda","family":"Jamshidi","sequence":"additional","affiliation":[{"name":"Genetics Section Molecular and Clinical Sciences Research Institute, St. George's, University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan G.","family":"Karimiani","sequence":"additional","affiliation":[{"name":"Genetics Section Molecular and Clinical Sciences Research Institute, St. George's, University of London  London UK"},{"name":"Department of Genetics Next Generation Polyclinic  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonna","family":"Komulainen\u2010Ebrahim","sequence":"additional","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Department of Children and Adolescents and Medical Research Center Oulu University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Kallankari","sequence":"additional","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Department of Children and Adolescents and Medical Research Center Oulu University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Mignot","sequence":"additional","affiliation":[{"name":"APHP.Sorbonne Universit\u00e9, D\u00e9partement de G\u00e9n\u00e9tique, H\u00f4pital Armand Trousseau and Groupe Hospitalier Piti\u00e9\u2010Salp\u00eatri\u00e8re Centre de R\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Depienne","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Groupe Hospitalier Piti\u00e9\u2010Salp\u00eatri\u00e8re APHP.Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Keren","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Groupe Hospitalier Piti\u00e9\u2010Salp\u00eatri\u00e8re APHP.Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Christine","family":"Nougues","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Neurop\u00e9diatrie APHP.Sorbonne Universit\u00e9, H\u00f4pital Trousseau  Trousseau France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-1132","authenticated-orcid":false,"given":"Zahra","family":"Alsahlawi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Salmaniya Medical Complex  Kingdom of Bahrain Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Romito","sequence":"additional","affiliation":[{"name":"Department of Medical Reporting and Genomics Centogene GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Medical Reporting and Genomics Centogene GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehran B.","family":"Toosi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics School of medicine, Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Genetics Section Molecular and Clinical Sciences Research Institute, St. George's, University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelia","family":"Tripolszki","sequence":"additional","affiliation":[{"name":"Department of Medical Reporting and Genomics Centogene GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9414-4555","authenticated-orcid":false,"given":"Peter","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Medical Reporting and Genomics Centogene GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Uusimaa","sequence":"additional","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Department of Children and Adolescents and Medical Research Center Oulu University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9544-1877","authenticated-orcid":false,"given":"Aida M.","family":"Bertoli\u2010Avella","sequence":"additional","affiliation":[{"name":"Department of Medical Reporting and Genomics Centogene GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-8229","authenticated-orcid":false,"given":"Peppi","family":"Koivunen","sequence":"additional","affiliation":[{"name":"Biocenter Oulu University of Oulu  Oulu Finland"},{"name":"Faculty of Biochemistry and Molecular Medicine 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Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.07.002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010019\u20100503\u20104"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.04.009"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0253\u201020.2020"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61885"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010021\u201002268\u20101"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010021\u201000932\u20108"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.25966"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22844"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.016542"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000244484.60489.50"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"}],"container-title":["Clinical 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