{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T10:27:33Z","timestamp":1781260053675,"version":"3.54.1"},"reference-count":67,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> Larsen syndrome is an autosomal dominant osteochondrodysplasia characterised by large-joint dislocations and craniofacial anomalies. Recently, Larsen syndrome was shown to be caused by missense mutations or small inframe deletions in <jats:italic>FLNB<\/jats:italic>, encoding the cytoskeletal protein filamin B. To further delineate the molecular causes of Larsen syndrome, 20 probands with Larsen syndrome together with their affected relatives were evaluated for mutations in <jats:italic>FLNB<\/jats:italic> and their phenotypes studied.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> Probands were screened for mutations in <jats:italic>FLNB<\/jats:italic> using a combination of denaturing high-performance liquid chromatography, direct sequencing and restriction endonuclease digestion. Clinical and radiographical features of the patients were evaluated.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results and discussion:<\/jats:bold> The clinical signs most frequently associated with a <jats:italic>FLNB<\/jats:italic> mutation are the presence of supernumerary carpal and tarsal bones and short, broad, spatulate distal phalanges, particularly of the thumb. All individuals with Larsen syndrome-associated <jats:italic>FLNB<\/jats:italic> mutations are heterozygous for either missense or small inframe deletions. Three mutations are recurrent, with one mutation, 5071G\u2192A, observed in 6 of 20 subjects. The distribution of mutations within the <jats:italic>FLNB<\/jats:italic> gene is non-random, with clusters of mutations leading to substitutions in the actin-binding domain and filamin repeats 13\u201317 being the most common cause of Larsen syndrome. These findings collectively define autosomal dominant Larsen syndrome and demonstrate clustering of causative mutations in <jats:italic>FLNB<\/jats:italic>.<\/jats:p>","DOI":"10.1136\/jmg.2006.043687","type":"journal-article","created":{"date-parts":[[2006,6,26]],"date-time":"2006-06-26T20:32:36Z","timestamp":1151353956000},"page":"89-98","source":"Crossref","is-referenced-by-count":99,"title":["A molecular and clinical study of Larsen syndrome caused by mutations in <i>FLNB<\/i>"],"prefix":"10.1136","volume":"44","author":[{"given":"Louise S","family":"Bicknell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Farrington-Rock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Shafeghati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Rump","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Alanay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Alembik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navid","family":"Al-Madani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Firth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Hassan","family":"Karimi-Nejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong Ae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Leask","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Maisenbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Moran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G","family":"Pappas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Prontera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomy","family":"de Ravel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Fryns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Sweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Fryer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Unger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L C","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph S","family":"Lachman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Rimoin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H","family":"Cohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Krakow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2006,6,26]]},"reference":[{"key":"2025101714191791000_44.2.89.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(50)80268-8"},{"key":"2025101714191791000_44.2.89.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(71)80014-8"},{"key":"2025101714191791000_44.2.89.3","first-page":"297","volume":"15","year":"1972","journal-title":"Ann Radiol (Paris)"},{"key":"2025101714191791000_44.2.89.4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1399-0004.1971.tb00260.x","volume":"2","year":"1971","journal-title":"Clin Genet"},{"key":"2025101714191791000_44.2.89.5","doi-asserted-by":"crossref","unstructured":"Oki T, Terashima Y, Murachi S, Nogami H. 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