{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:37:09Z","timestamp":1791250629003,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"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":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Branchio\u2010oto\u2010renal syndrome is a heterogeneous disorder inherited in an autosomal dominant pattern, characterized by branchial arch abnormalities, hearing loss and renal abnormalities, with mutations in <jats:italic>EYA1<\/jats:italic> reported in 30\u201370% of patients. We have applied a molecular testing strategy of sequencing of the complete coding region\/flanking intronic regions and multiple ligation probe amplification analysis of <jats:italic>EYA1<\/jats:italic> to a pediatric branchio\u2010oto\u2010renal proband cohort. <jats:italic>EYA1<\/jats:italic> mutations were identified in 82% (14\/17) of the probands. We also describe a novel recurrent <jats:italic>EYA1<\/jats:italic> mutation c.867\u2009+\u20095G\u2009&gt;\u2009A found in five unrelated affected patients. RNA analysis showed that c.867\u2009+\u20095G\u2009&gt;\u2009A affects <jats:italic>EYA1<\/jats:italic> splicing, producing an aberrant mRNA transcript lacking exon 8 and resulting in premature termination in exon 9. The aberrant transcript was present at approximately 50% level of wild\u2010type <jats:italic>EYA1<\/jats:italic> mRNA in fibroblasts, and is predicted to encode an EYA1 protein retaining the amino terminal transcriptional coactivator region but lacking the conserved carboxy terminal Eya phosphatase domain. Patients with the c.867\u2009+\u20095G\u2009&gt;\u2009A mutation were found to have more severe renal abnormalities than probands with other mutations in this cohort. Analysis of the c.867\u2009+\u20095G\u2009&gt;\u2009A mutation suggests that certain transcripts of <jats:italic>EYA1<\/jats:italic> escape nonsense\u2010mediated decay and encode truncated EYA proteins that may be capable of dominant\u2010negative interactions producing distinct phenotypic features within the branchio\u2010oto\u2010renal spectrum. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32679","type":"journal-article","created":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T18:57:21Z","timestamp":1234292241000},"page":"322-327","source":"Crossref","is-referenced-by-count":21,"title":["A recurrent <i>EYA1<\/i> mutation causing alternative RNA splicing in branchio\u2010oto\u2010renal syndrome: Implications for molecular diagnostics and disease mechanism"],"prefix":"10.1002","volume":"149A","author":[{"given":"Tracy L.","family":"Stockley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Mendoza\u2010Londono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan J.","family":"Propst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandi","family":"Sodhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Dupuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake C.","family":"Papsin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0297-157"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.13.2247"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-005-1262-7"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20048"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/513322"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1322"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-006-0384-7"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20400"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02083"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2004.00318.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20151"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-006-0041-6"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20691"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000177032.98386.20"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)12:3<153::AID-HUMU3>3.0.CO;2-I"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308475101"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201900"},{"key":"e_1_2_6_19_1","unstructured":"SmithRJH. (Updated 27 March2008). Branchiootorenal Syndrome. In: Gene Reviews at GeneTests: Medical Genetics Information Resource (database online). Copyright University of Washington Seattle. 1997\u20132008. Available athttp:\/\/www.genetests.org. Accessed 21 July 2008."},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-004-4044-3"}],"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.32679","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.32679","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T04:00:35Z","timestamp":1697601635000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.32679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,10]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,3]]}},"alternative-id":["10.1002\/ajmg.a.32679"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.32679","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,10]]}}}