{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T10:34:28Z","timestamp":1711708468462},"reference-count":12,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>A 4-yr-old female with congenital knee dislocations and joint laxity was noted to have a strong maternal family history comprising multiple individuals with knee problems and clubfeet. As the knee issues were the predominant clinical features, clinical testing included sequencing of <jats:italic>LMX1B<\/jats:italic>, <jats:italic>TBX2<\/jats:italic>, and <jats:italic>TBX4<\/jats:italic>, which identified no significant variants. Research genome sequencing was performed in the proband, parents, and maternal grandfather. A heterozygous in-frame deletion in <jats:italic>FLNB<\/jats:italic> c. 5468_5470delAGG, which predicts p.(Glu1823del), segregated with the disease. The variant is rare in the gnomAD database, removes a residue that is evolutionarily conserved, and is predicted to alter protein length. Larsen syndrome may present with pathology that primarily involves one joint and thus may be difficult to differentiate clinically from other skeletal dysplasias or arthrogryposis syndromes. The p.(Glu1823del) variant maps to a filamin repeat domain where other disease-causing variants are clustered, consistent with a probable gain-of-function mechanism. It has reportedly been observed in two individuals in the gnomAD database, suggesting that mild presentations of Larsen syndrome, like the individual reported here, may be underdiagnosed in the general population.<\/jats:p>","DOI":"10.1101\/mcs.a004176","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T19:35:24Z","timestamp":1576265724000},"page":"a004176","source":"Crossref","is-referenced-by-count":2,"title":["Novel in-frame <i>FLNB<\/i> deletion causes Larsen syndrome in a three-generation pedigree"],"prefix":"10.1101","volume":"5","author":[{"given":"Scott E.","family":"Hickey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C.","family":"Koboldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa Mihalic","family":"Mosher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Brennan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth A.","family":"Schmalz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Crist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim L.","family":"McBride","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent H.","family":"Adler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard K.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"246","published-online":{"date-parts":[[2019,12,13]]},"reference":[{"key":"2021112406080313000_5.6.a004176.1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.043687"},{"key":"2021112406080313000_5.6.a004176.2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22012"},{"key":"2021112406080313000_5.6.a004176.3","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-016-0276-4"},{"key":"2021112406080313000_5.6.a004176.4","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0572-2"},{"key":"2021112406080313000_5.6.a004176.5","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a002410"},{"key":"2021112406080313000_5.6.a004176.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng1319"},{"key":"2021112406080313000_5.6.a004176.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(50)80268-8"},{"key":"2021112406080313000_5.6.a004176.8","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm114"},{"key":"2021112406080313000_5.6.a004176.9","unstructured":"Robertson S . 2017. FLNB-related disorders. In GeneReviews (ed. Adam MP , Ardinger HH , Pagon RA , ), pp. 1\u201319. University of Washington, Seattle."},{"key":"2021112406080313000_5.6.a004176.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.06.009"},{"key":"2021112406080313000_5.6.a004176.11","doi-asserted-by":"publisher","DOI":"10.1038\/35052082"},{"key":"2021112406080313000_5.6.a004176.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608360104"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a004176","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T14:13:24Z","timestamp":1637763204000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a004176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":12,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,12,13]]},"published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1101\/mcs.a004176"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a004176","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]}}}