{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:51:23Z","timestamp":1788522683025,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK117854"],"award-info":[{"award-number":["R01 DK117854"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>ALDH1L2, a mitochondrial enzyme in folate metabolism, converts 10\u2010formyl\u2010THF (10\u2010formyltetrahydrofolate) to THF (tetrahydrofolate) and CO<jats:sub>2<\/jats:sub>. At the cellular level, deficiency of this NADP<jats:sup>+<\/jats:sup>\u2010dependent reaction results in marked reduction in NADPH\/NADP<jats:sup>+<\/jats:sup> ratio and reduced mitochondrial ATP. Thus far, a single patient with biallelic <jats:italic>ALDH1L2<\/jats:italic> variants and the phenotype of a neurodevelopmental disorder has been reported. Here, we describe another patient with a neurodevelopmental disorder associated with a novel homozygous missense variant in <jats:italic>ALDH1L2<\/jats:italic>, Pro133His. The variant caused marked reduction in the ALDH1L2 enzyme activity in skin fibroblasts derived from the patient as probed by 10\u2010FDDF, a stable synthetic analog of 10\u2010formyl\u2010THF. Additional associated abnormalities in these fibroblasts include reduced NADPH\/NADP<jats:sup>+<\/jats:sup> ratio and pool of mitochondrial ATP, upregulated autophagy and dramatically altered metabolomic profile. Overall, our study further supports a link between ALDH1L2 deficiency and abnormal neurodevelopment in humans.<\/jats:p>","DOI":"10.1111\/cge.14479","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T10:12:01Z","timestamp":1704795121000},"page":"488-498","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Further delineation of the phenotypic and metabolomic profile of <i>ALDH1L2<\/i>\u2010related neurodevelopmental disorder"],"prefix":"10.1111","volume":"105","author":[{"given":"Mikyoung","family":"You","sequence":"first","affiliation":[{"name":"UNC Nutrition Research Institute  Kannapolis North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan E.","family":"Shamseldin","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Center for Genomic Medicine King Faisal Specialist Hospital and Research Center (KFSHRC)  Riyadh 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