{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:28:02Z","timestamp":1769070482507,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T00:00:00Z","timestamp":1626480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001515","name":"Cure Kids","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathogenic variation in the X\u2010linked gene <jats:italic>FLNA<\/jats:italic> causes a wide range of human developmental phenotypes. Loss\u2010of\u2010function is usually male embryonic\u2010lethal, and most commonly results in a neuronal migration disorder in affected females. Gain\u2010of\u2010function variants cause a spectrum of skeletal dysplasias that present with variable additional, often distinctive, soft\u2010tissue anomalies in males and females. Here we present two, unrelated, male individuals with novel, intronic variants in <jats:italic>FLNA<\/jats:italic> that are predicted to be pathogenic. Their phenotypes are reminiscent of the gain\u2010of\u2010function spectrum without the skeletal manifestations. Most strikingly, they manifest urethral anomalies, cardiac malformations, and keloid scarring, all commonly encountered features of frontometaphyseal dysplasia. Both variants prevent inclusion of exon 40 into the <jats:italic>FLNA<\/jats:italic> transcript, predicting the in\u2010frame deletion of 42 amino acids, however the abundance of FLNA protein was equivalent to that observed in healthy individuals. Loss of these 42 amino acids removes sites that mediate key FLNA functions, including binding of some ligands and phosphorylation. This phenotype further expands the spectrum of the <jats:italic>FLNA<\/jats:italic> filaminopathies.<\/jats:p>","DOI":"10.1002\/ajmg.a.62424","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T12:16:02Z","timestamp":1626524162000},"page":"3675-3682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exon skip\u2010inducing variants in <scp><i>FLNA<\/i><\/scp> in an attenuated form of frontometaphyseal dysplasia"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-0232","authenticated-orcid":false,"given":"Emma M.","family":"Wade","sequence":"first","affiliation":[{"name":"Department of Women's and Children's Health Dunedin School of Medicine, University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zandra A.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Dunedin School of Medicine, University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Dunedin School of Medicine, University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Gimenez","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayley","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Dunedin School of Medicine, University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Dunedin School of Medicine, University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossana","family":"Sanchez Russo","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Emory University  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cara M.","family":"Skraban","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"The Roberts Individualized Medical Genetics Center Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Bedoukian","sequence":"additional","affiliation":[{"name":"The Roberts Individualized Medical Genetics Center Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5181-7809","authenticated-orcid":false,"given":"Stephen P.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Dunedin School of Medicine, University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw343"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37491"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10430"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80651-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.3.1089"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-020-0973-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi2003229"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23355"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181f0ae47"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.01.011"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.622621"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601827"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1002\/ajmg.a.37567","article-title":"A distinct X\u2010linked syndrome involving joint contractures, keloids, large optic cup\u2010to\u2010disc ratio, and renal stones results from a filamin A (FLNA) mutation","volume":"170","author":"Lah M.","year":"2015","journal-title":"American Journal of Medical Genetics Part A"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.5.2.14401"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-365601"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.119"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00020a020"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-004-0187-y"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl125"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201654"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31322"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1119"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10265"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(01)00072-6"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24002"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62424","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62424","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62424","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T10:17:08Z","timestamp":1692958628000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62424"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,17]]},"references-count":26,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/ajmg.a.62424"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62424","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,17]]},"assertion":[{"value":"2021-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}