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Pathogenic variants in fibrillin-2, encoded by <jats:italic>FBN2<\/jats:italic>, have mainly been associated with congenital contractural arachnodactyly but in a few cases also with brachydactyly.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We recruited two families with index patients presenting with short stature (heights \u22643 SD scores), brachydactyly, joint contractures and facial dysmorphism as major features. In Family 2, the proband and father also had carpal tunnel syndrome. Radiographs showed signs of mild skeletal dysplasia with short long bones, brachydactyly and mild metaphyseal and vertebral irregularity. Whole genome sequencing revealed novel variants in the <jats:italic>FBN2<\/jats:italic> gene that segregated with the phenotype: in Family 1, a novel heterozygous missense variant c.4862G&gt;A, p.(Cys1621Tyr) and in Family 2, a novel heterozygous deletion of exons 9\u201311. The missense variant affects a highly conserved residue and is predicted to be deleterious by most in silico tools. The <jats:italic>FBN2<\/jats:italic> deletion affects a well-conserved region and leads to loss of the transforming growth factor \u03b2 binding-like 2 domain and part of the calcium-binding epidermal growth factor-like domain.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our findings suggest that short stature and mild skeletal dysplasia might be part of the spectrum of <jats:italic>FBN2-<\/jats:italic>related phenotypes. The study supports the role of <jats:italic>FBN2<\/jats:italic> variants in growth failure and expands the molecular spectrum of <jats:italic>FBN2<\/jats:italic> variants.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2024-110533","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T13:41:18Z","timestamp":1744119678000},"page":"436-440","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Short stature, brachydactyly and joint contractures associated with novel <i>FBN2<\/i> variants in two families"],"prefix":"10.1136","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2708-0878","authenticated-orcid":false,"given":"Petra","family":"Loid","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital, University of Helsinki and Helsinki University Hospital, and Folkh\u00e4lsan Research Center, Genetics Research Program, Helsinki, Uusimaa, Finland"},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Lennartsson","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Muurinen","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, University of Helsinki and Helsinki University Hospital, and Folkh\u00e4lsan Research Center, Genetics Research Program, Helsinki, Uusimaa, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1408-9272","authenticated-orcid":false,"given":"Alice","family":"Costantini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakshi","family":"Vats","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Lodefalk","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"},{"name":"University Health Care Research Centre, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"},{"name":"Division of Paediatric Endocrinology and Center for Molecular Medicine, Department of Women's and Children's health, Karolinska Institutet and University Hospital (ERN BOND, Endo-ERN), Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, University of Helsinki and Helsinki University Hospital, and Folkh\u00e4lsan Research Center, Genetics Research Program, Helsinki, Uusimaa, Finland"},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"2025101505050564000_62.7.436.1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14465"},{"key":"2025101505050564000_62.7.436.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-120922-094107"},{"key":"2025101505050564000_62.7.436.3","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201003089"},{"key":"2025101505050564000_62.7.436.4","unstructured":"Callewaert B . 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