{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T08:06:04Z","timestamp":1774771564895,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T00:00:00Z","timestamp":1597795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recessive variants in the <jats:italic>GLDN<\/jats:italic> gene, which encodes the gliomedin protein and is involved in nervous system development, have recently been associated with Arthrogryposis Multiplex Congenita (AMC), a heterogenous condition characterized by congenital contractures of more than one joint. Two cohorts of patients with <jats:italic>GLDN<\/jats:italic>\u2010associated AMC have previously been described, evolving the understanding of the condition from lethal to survivable with the provision of significant neonatal support. Here, we describe one additional patient currently living with the syndrome, having one novel variant, p.Leu365Phe, for which we provide functional data supporting its pathogenicity. We additionally provide experimental data for four other previously reported variants lacking functional evidence, including p.Arg393Lys, the second variant present in our patient. We discuss unique and defining clinical features, adding calcium\u2010related findings which appear to be recurrent in the <jats:italic>GLDN<\/jats:italic> cohort. Finally, we compare all previously reported patients and draw new conclusions about scope of illness, with emphasis on the finding of pulmonary hypoplasia, suggesting that AMC secondary to <jats:italic>GLDN<\/jats:italic> variants may be best fitted under the umbrella of fetal akinesia deformation sequence (FADS).<\/jats:p>","DOI":"10.1002\/ajmg.a.61783","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T03:14:25Z","timestamp":1598584465000},"page":"2291-2296","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The latest <scp>FADS<\/scp>: Functional analysis of <scp><i>GLDN<\/i><\/scp> patient variants and classification of <scp><i>GLDN<\/i><\/scp>\u2010associated <scp>AMC<\/scp> as a type of viable fetal akinesia deformation sequence"],"prefix":"10.1002","volume":"182","author":[{"given":"Emily K.","family":"Mis","sequence":"first","affiliation":[{"name":"Pediatric Genomics Discovery Program, Department of Pediatrics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samir","family":"Al\u2010Ali","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Department of Pediatrics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weizhen","family":"Ji","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Department of Pediatrics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Spencer\u2010Manzon","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Department of Pediatrics Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Genetics Yale University School of Medicine  New Haven 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