{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T09:19:30Z","timestamp":1766481570297,"version":"3.48.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek0109760"],"award-info":[{"award-number":["JP24ek0109760"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Congenital Anomalies"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sj\u00f6gren\u2010Larsson syndrome (SLS) is an autosomal recessive leukodystrophy characterized by ichthyosis, intellectual disability, and progressive spastic paralysis caused by biallelic pathogenic variants in the\n                    <jats:italic>ALDH3A2<\/jats:italic>\n                    gene that encodes the fatty aldehyde dehydrogenase, fatty aldehyde dehydrogenase (FALDH); FALDH catalyzes several metabolic reactions involved in fatty aldehyde oxidation. Only a few studies have been performed to determine the lipid profile of patients with SLS. In a previous postmortem study of the brain of a 65\u2010year\u2010old patient with SLS, lipidomic analysis revealed an accumulation of long\u2010chain unsaturated ether lipid species in the white matter and gray matter. In the present study, we established a disease model using patient\u2010derived neuronal and oligodendrocyte lineage cells to analyze the lipid metabolism and gene expression profiles in SLS. To achieve this, we generated induced pluripotent stem cells (iPSCs) from two patients with the SLS phenotype carrying previously known\n                    <jats:italic>ALDH3A2<\/jats:italic>\n                    pathogenic variants: One was a compound heterozygote (c.1339A&gt;G:p.(Lys447Glu) and c.57_132dup:p.(Ile45Serfs*34)) and the other was a homozygote (c.1339A&gt;G: p.(Lys447Glu)). The FALDH activity was almost zero in the SLS\u2010iPSC lines established from both patients. Phospholipid analysis of neurospheres, and oligospheres (spheres enriched with oligodendrocyte\u2010lineage cells) derived from the iPSCs by liquid chromatography\u2010mass spectrometry showed accumulation of ether phospholipids in the Sj\u00f6gren\u2010Larsson patient\u2010derived neurospheres and oligospheres. The results are consistent with the previously reported accumulation of ether lipids in the postmortem brain tissue of an SLS patient. Therefore, iPSCs and iPSC\u2010derived neurospheres and oligospheres established from SLS patients can be useful tools for future pathological analysis of the central nervous system pathophysiology in SLS.\n                  <\/jats:p>","DOI":"10.1111\/cga.12587","type":"journal-article","created":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T19:34:02Z","timestamp":1733081642000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Accumulation of ether phospholipids in induced pluripotent stem cells and oligodendrocyte\u2010lineage cells established from patients with Sj\u00f6gren\u2010Larsson syndrome"],"prefix":"10.1111","volume":"65","author":[{"given":"Yu","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Genetics Gunma Children's Medical Center  Shibukawa Japan"},{"name":"Department of Physiology Keio University School of Medicine  Tokyo Japan"},{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo Japan"},{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1932-9482","authenticated-orcid":false,"given":"Hironobu","family":"Okuno","sequence":"additional","affiliation":[{"name":"Department of Physiology Keio University School of Medicine  Tokyo Japan"},{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo Japan"},{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"},{"name":"Department of Pediatrics and Adolescent Medicine Tokyo Medical University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzumi","family":"Tokuoka","sequence":"additional","affiliation":[{"name":"Department of Lipidomics, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Kita","sequence":"additional","affiliation":[{"name":"Department of Lipidomics, Graduate School of Medicine The University of Tokyo  Tokyo Japan"},{"name":"Life Sciences Core Facility, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsukasa","family":"Sanosaka","sequence":"additional","affiliation":[{"name":"Department of Physiology Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Kohyama","sequence":"additional","affiliation":[{"name":"Department of Physiology Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-7748","authenticated-orcid":false,"given":"Kenji","family":"Kurosawa","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Sakai","sequence":"additional","affiliation":[{"name":"Division of Health Sciences Osaka University Graduate School of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyuki","family":"Miya","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takao","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo Japan"},{"name":"Center for Developmental Neurology Shin\u2010yurigaoka General Hospital  Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyuki","family":"Okano","sequence":"additional","affiliation":[{"name":"Department of Physiology Keio University School of Medicine  Tokyo Japan"},{"name":"Keio University Regenerative Medicine Research Center  Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20181"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196\u201052"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/21678707.2016.1154453"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403\u2010009\u20101022\u2010y"},{"issue":"8","key":"e_1_2_8_6_1","first-page":"1561","article-title":"MR of the brain in Sj\u00f6gren\u2010Larsson syndrome","volume":"18","author":"Van Mieghem 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