{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:31:19Z","timestamp":1790854279990,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Loss\u2010of\u2010function variants in\n                    <jats:italic>FREM1<\/jats:italic>\n                    have been demonstrated in Manitoba oculotrichoanal syndrome (MOTA) and bifid nose, renal agenesis, and anorectal malformations (BNAR) syndrome, but the broader phenotypic spectrum of\n                    <jats:italic>FREM1<\/jats:italic>\n                    variants remains incompletely characterized. In this study, we report compound heterozygous variants in a prenatal case of bilateral renal agenesis. Exome sequencing revealed biallelic\n                    <jats:italic>FREM1<\/jats:italic>\n                    variants: c.5622G&gt;A (p.Trp1874*) and c.3274+4A&gt;G (p.Gly1030_Ile1091del). Minigene and bioinformatic analyses confirmed that the splice site variant induces aberrant splicing and alters transcriptional expression levels. This finding underscores the crucial role of non\u2010canonical splice site variants in\n                    <jats:italic>FREM1<\/jats:italic>\n                    in the pathogenesis of bilateral renal agenesis.\n                  <\/jats:p>","DOI":"10.1111\/cge.70016","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T02:54:44Z","timestamp":1751511284000},"page":"194-198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non\u2010Canonical Splice Site Variant in\n                    <i>FREM1<\/i>\n                    Result in Fetal Renal Agenesis"],"prefix":"10.1111","volume":"109","author":[{"given":"Xingyu","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Maternal and Child Care Service Center of Linxia hui Autonomous Prefecture  Linxia China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chulong","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6516"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/crpm-2021-0063"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpm-2016-0367"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.09.026"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-024-03178-4"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35736"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008200802148025"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/24.10.834"},{"key":"e_1_2_10_10_1","first-page":"1301","article-title":"Evidence for Additional FREM1 Heterogeneity in Manitoba Oculotrichoanal Syndrome","volume":"18","author":"Mateo R. 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