{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T15:27:49Z","timestamp":1772206069229,"version":"3.50.1"},"reference-count":12,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T00:00:00Z","timestamp":1466985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>Hennekam lymphangiectasia\u2013lymphedema syndrome is an autosomal recessive disorder, with 25% of patients having mutations in <jats:italic>CCBE1<\/jats:italic>. We identified a family with two brothers presenting with primary lymphedema, and performed exome sequencing to determine the cause of their disease. Analysis of four family members showed that both affected brothers had the same rare compound heterozygous mutations in <jats:italic>CCBE1<\/jats:italic>. The presumed paternally inherited NM_133459.3:c.310G&gt;A; p.(Asp104Asn), lies adjacent to other known pathogenic <jats:italic>CCBE1<\/jats:italic> mutations, while the maternally inherited NM_133459.3:c.80T&gt;C; p.(Leu27Pro) lies in the CCBE1 signal peptide, which has not previously been associated with disease. Functional analysis in a zebrafish model of lymphatic disease showed that both mutations lead to CCBE1 loss of function, confirming the pathogenicity of these variants and expanding the genotypic spectrum of lymphatic disorders. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37803","type":"journal-article","created":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T11:16:50Z","timestamp":1467026210000},"page":"2694-2697","source":"Crossref","is-referenced-by-count":9,"title":["Expanding the genotypic spectrum of <i>CCBE1<\/i> mutations in Hennekam syndrome"],"prefix":"10.1002","volume":"170","author":[{"given":"Joanna","family":"Crawford","sequence":"first","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil I.","family":"Bower","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin M.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan J.","family":"Taft","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia"},{"name":"Illumina, Inc. San Diego California"},{"name":"School of Medicine and Health The George Washington University Washington District of Columbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Gabbett","sequence":"additional","affiliation":[{"name":"Genetic Health Queensland Royal Brisbane and Women's Hospital Brisbane Australia"},{"name":"School of Medicine The University of Queensland Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"McGaughran","sequence":"additional","affiliation":[{"name":"Genetic Health Queensland Royal Brisbane and Women's Hospital Brisbane Australia"},{"name":"School of Medicine The University of Queensland Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cas","family":"Simons","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,6,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.484"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1159\/000342486","article-title":"Evaluation of clinical manifestations in patients with severe lymphedema with and without CCBE1 mutations","volume":"4","author":"Alders M","year":"2013","journal-title":"Mol Syndromol"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1456-y"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2545"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01731.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9085"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320340429"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.321"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.039990"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0225-6"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000354097"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3153"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37803","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37803","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T02:17:12Z","timestamp":1694312232000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,27]]},"references-count":12,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1002\/ajmg.a.37803"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37803","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,27]]}}}