{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:44:06Z","timestamp":1791110646405,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T00:00:00Z","timestamp":1549324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011264","name":"FP7 People: Marie-Curie Actions","doi-asserted-by":"publisher","award":["CardioNet ITN 2011 GA289600"],"award-info":[{"award-number":["CardioNet ITN 2011 GA289600"]}],"id":[{"id":"10.13039\/100011264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Follistatin\u2010like 1 (Fstl1) is a glycoprotein expressed throughout embryonic development. Homozygous loss of Fstl1 in mice results in skeletal and respiratory defects, leading to neonatal death due to a collapse of the trachea. Furthermore, Fstl1 conditional deletion from the endocardial\/endothelial lineage results in postnatal death due to heart failure and profound atrioventricular valve defects. Here, we investigated patients with phenotypes similar to the phenotypes observed in the transgenic mice, for variants in <jats:italic>FSTL1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 69 genetically unresolved patients were selected with the following phenotypes: campomelic dysplasia (12), small patella syndrome (2), BILU (1), and congenital heart disease patients (54), of which 16 also had kyphoscoliosis, and 38 had valve abnormalities as their main diagnosis. Using qPCR, none of 69 patients showed copy number variations in <jats:italic>FSTL1<\/jats:italic>. The entire gene body, including microRNA\u2010198 and three validated microRNA\u2010binding sites, were analyzed using Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No variants were found in the coding region. However, 8 intronic variants were identified that differed significantly in their minor allele frequency compared to controls. Variant rs2272515 was found to significantly correlate (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) with kyphoscoliosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that pathogenic variants in <jats:italic>FSTL1<\/jats:italic> are unlikely to be responsible for skeletal or atrioventricular valve anomalies in humans.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.567","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T23:04:51Z","timestamp":1549407891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identifying pathogenic variants in the Follistatin\u2010like 1 gene (<i>FSTL1<\/i>) in patients with skeletal and atrioventricular valve disorders"],"prefix":"10.1002","volume":"7","author":[{"given":"Stuti","family":"Prakash","sequence":"first","affiliation":[{"name":"Department of Medical Biology Amsterdam UMC, location AMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mattiotti","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Amsterdam UMC, location AMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Sylva","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Amsterdam UMC, location AMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J. M.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Cardiology Amsterdam UMC, location AMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex V.","family":"Postma","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Amsterdam UMC, location AMC Amsterdam The Netherlands"},{"name":"Department of Clinical Genetics Amsterdam UMC, location AMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3837-8055","authenticated-orcid":false,"given":"Maurice J. 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