{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T18:28:50Z","timestamp":1754159330028,"version":"3.41.2"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901383","82101515"],"award-info":[{"award-number":["81901383","82101515"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>SOST<\/jats:italic> encodes a secreted glycoprotein that is similar in sequence to the differential screening\u2010selected gene aberrative in neuroblastoma (DAN) family of bone morphogenetic protein (BMP) antagonists. Pathogenic variants in the <jats:italic>SOST<\/jats:italic> gene result in sclerosteosis, van Buchem disease (VBD), or craniodiaphyseal dysplasia. <jats:italic>SOST<\/jats:italic>\u2010related genetic disorders are very rare, and limited studies have reported variants associated with sclerosteosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical tests such as magnetic resonance imaging (MRI), computed tomography (CT), emission computed tomography (ECT), electromyogram (EMG), routine blood tests, and physical examinations were conducted for the proband. Trio\u2010whole exome sequencing (Trio\u2010WES) was performed, and the rare variants (allele frequency\u2009&lt;\u20090.01) in the exon and splicing regions were selected for further pathogenic evaluation. Candidate pathogenic variants were validated through Sanger sequencing. The wild and mutant <jats:italic>SOST<\/jats:italic> sequences were cloned into the pcDNA3.1 expression vector, and the RNA and protein expression levels were investigated in the HEK293T cell line.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, we present a case study of a proband who displays abnormal facial expressions accompanied by numbness. The results of the brain MRI show thickening of the skull and disappearance of the diplopia signal. The temporal bone CT scan indicates diffuse osteosclerosis affecting the bilateral ossicular chains and internal auditory meatus, as well as stenosis of the bilateral internal auditory meatus. Trio\u2010WES sequencing detected a novel homozygous variant in the proband: NM_025237.3(<jats:italic>SOST<\/jats:italic>): c.327C&gt;A (p.Cys109*), which was also validated in his sister from the same family. According to the ACMG guidelines, the variant is classified as \u201clikely pathogenic.\u201d The in\u00a0vitro experiments demonstrated that the variant caused a decrease in <jats:italic>SOST<\/jats:italic> expression at RNA and protein level and produced a truncated protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The report presents new evidence for the clinical diagnosis of <jats:italic>SOST<\/jats:italic>\u2010related facial numbness and expands the variant spectrum of <jats:italic>SOST<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70109","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T01:30:23Z","timestamp":1751506223000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Loss of Function Variant in <scp><i>SOST<\/i><\/scp> From Chinese Family Results in Sclerosteosis 1"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1527-0383","authenticated-orcid":false,"given":"Yufan","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xintao","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Gu","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5165-2613","authenticated-orcid":false,"given":"Pu","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueting","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chudi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-407X","authenticated-orcid":false,"given":"Jianhua","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"},{"name":"Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.02.019"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.5.537"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.2.91"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/302416"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/318811"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58020202"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-0947-3"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-022-06523-7"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/03000605231193293"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2023-0325"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094751"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.10.009"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2017.10.005"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10401"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-020-01176-0"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1794"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T06:42:20Z","timestamp":1753425740000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":20,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/mgg3.70109"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70109","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2024-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70109"}}