{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:29:49Z","timestamp":1788866989929,"version":"build-2803163510"},"reference-count":8,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:p>We report a further case of spondylometaphyseal dysplasia \u2013 corner fracture type due to the fibronectin-1 gene (<jats:italic toggle=\"yes\">SMD-FN1<\/jats:italic>) in a child originally thought to have metaphyseal chondrodysplasia-Brussels type (MCD Brussels). We highlight phenotypic differences with the SMD-FN1 published reports. This case is unique in terms of the method of molecular confirmation. Findings from the 100 000 Genomes Project were originally negative (in both tier 1 and 2); however, subsequent reanalysis, initiated by an automated search for new gene-disease associations in PanelApp, highlighted a candidate diagnostic variant. Our child had short stature, facial dysmorphism, spondylometaphyseal dysplasia and corner fractures and a heterozygous de novo missense variant in <jats:italic toggle=\"yes\">FN1<\/jats:italic> (c.675C&gt;G p.(Cys225Trp), which was likely pathogenic. The variant matched the clinical and radiological features and a diagnosis of SMD-FN1 was confirmed. We explore the diagnostic journey of this patient, compare her findings with the previous 15 patients reported with SMD-FN1 and discuss the diagnostic utility of automated reanalysis. We consider differences and similarities between MCD Brussels and SMD-FN1, by reviewing literature on both conditions and assess whether they are in fact the same disorder.<\/jats:p>","DOI":"10.1097\/mcd.0000000000000369","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T01:28:18Z","timestamp":1614389298000},"page":"154-158","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Automated reanalysis, a novel way to diagnose an ultra-rare condition: Fibronectin-1-related spondylometaphyseal dysplasia (SMD-FN1)"],"prefix":"10.1097","volume":"30","author":[{"given":"Ataf H.","family":"Sabir","sequence":"first","affiliation":[{"name":"Clinical Genetics Registrar, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust (London), Birmingham Women\u2019s and Children\u2019s Hospital NHS Trust & Birmingham Health Partners"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhi","family":"Singhal","sequence":"additional","affiliation":[{"name":"Medical Student, University of Birmingham, Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Man","sequence":"additional","affiliation":[{"name":"Medical Student, University of Birmingham, Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana Ekuntan","family":"Mensah","sequence":"additional","affiliation":[{"name":"Trainee Clinical Bioinformatician, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Wook","family":"Ahn","sequence":"additional","affiliation":[{"name":"East England GLH Bioinformatics Lead, Cambridge University Hospitals NHS FT, Addenbrooke\u2019s Hospital, Cambridge"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira S.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Consultant Paediatric Endocrinologist"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melita","family":"Irving","sequence":"additional","affiliation":[{"name":"Consultant Clinical Geneticist, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"R1-20250524","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/cge.13424","article-title":"Mechanistic insights into the cellular effects of a novel FN1 variant associated with a spondylometaphyseal dysplasia.","volume":"94","author":"Cadoff","year":"2018","journal-title":"Clin Genet"},{"key":"R2-20250524","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.bone.2018.12.020","article-title":"Novel fibronectin mutations and expansion of the phenotype in spondylometaphyseal dysplasia 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