{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:06:13Z","timestamp":1790064373332,"version":"4.0.1"},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007797","name":"Helsingin Yliopisto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007797","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fetal akinesia deformation sequence (FADS) and lethal multiple pterygium syndrome (LMPS) are clinically overlapping syndromes manifesting with reduced or absent fetal movement, arthrogryposis, and several anomalies during fetal life. The etiology of these syndromes is heterogeneous, and in many cases it remains unknown. In order to determine the genetic etiology of FADS in two fetuses with fetal akinesia, arthrogryposis, edema, and partial cleft palate, we utilized exome sequencing. Our investigations revealed a homozygous nonsense variant [c.1116C&gt;A, p.(Cys372Ter)] in the <jats:italic>SLC18A3<\/jats:italic> gene, which encodes for the vesicular acetylcholine transporter (VAChT) responsible for active transport of acetylcholine in the neuromuscular junction. This is the first description of a nonsense variant in the <jats:italic>SLC18A3<\/jats:italic> gene, as only missense variants and whole gene deletions have been previously identified in patients. The previously detected <jats:italic>SLC18A3<\/jats:italic> defects have been associated with congenital myasthenic syndromes, and therefore our findings extend the clinical spectrum of <jats:italic>SLC18A3<\/jats:italic> defects to severe prenatal phenotypes. Our findings suggest that nonsense variants in <jats:italic>SLC18A3<\/jats:italic> cause a more severe phenotype than missense variants and are in line with previous studies showing a lethal phenotype in VAChT knockout mice. Our results underline the importance of including <jats:italic>SLC18A3<\/jats:italic> sequencing in the differential diagnostics of fetuses with arthrogryposis, FADS, or LMPS of unknown etiology.<\/jats:p>","DOI":"10.1002\/ajmg.a.61186","type":"journal-article","created":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T22:26:46Z","timestamp":1557181606000},"page":"1362-1365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>SLC18A3<\/i> variants lead to fetal akinesia deformation sequence early in pregnancy"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-7124","authenticated-orcid":false,"given":"Anna H.","family":"Hakonen","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, HUSLAB University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Polvi","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, HUSLAB University of Helsinki and Helsinki University Hospital  Helsinki Finland"},{"name":"Institute for Molecular Medicine Finland FIMM, University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Saloranta","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, HUSLAB University of Helsinki and Helsinki University Hospital  Helsinki Finland"},{"name":"Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Paetau","sequence":"additional","affiliation":[{"name":"Department of Pathology HUSLAB, University of Helsinki and Helsinki University Hospital  Helsinki 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