{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:58:50Z","timestamp":1789955930086,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,6,17]],"date-time":"2002-06-17T00:00:00Z","timestamp":1024272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[2002,7,22]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CHARGE is a nonrandom association of ocular coloboma, congenital heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear anomalies including deafness. The cause of CHARGE remains unknown; however, there is considerable evidence of an underlying genetic basis, as discussed by Tellier et al. [<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib26\">1996<\/jats:ext-link>: Clin Genet 50:548\u2013550; 1998: Am J Med Genet 76:402\u2013409] and by Martin et al. [<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib18\">2001<\/jats:ext-link>: Am J Med Genet 99:115\u2013119]. Based on the ocular, cardiac, and craniofacial expression pattern of <jats:italic>Pitx2<\/jats:italic>, a homeodomain transcription factor, and the pleiotropic effects of loss of <jats:italic>PITX2<\/jats:italic> function in both mouse and human, we hypothesized that <jats:italic>PITX2<\/jats:italic> mutations may contribute to the multiple phenotypic anomalies present in CHARGE individuals. By direct sequencing of DNA from 29 individuals with CHARGE, we did not identify any mutations in <jats:italic>PITX2<\/jats:italic>. We did, however, identify two <jats:italic>PITX2<\/jats:italic> sequence polymorphisms. Large deletions of <jats:italic>PITX2<\/jats:italic> were excluded in most patients by heterozygosity in at least one of several polymorphic markers near the <jats:italic>PITX2<\/jats:italic> locus. Together, these data indicate that <jats:italic>PITX2<\/jats:italic> mutations are unlikely to be a major contributing cause of the multiple anomalies present in individuals with CHARGE. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.10473","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T11:52:48Z","timestamp":1033905168000},"page":"27-30","source":"Crossref","is-referenced-by-count":28,"title":["Exclusion of <i>PITX2<\/i> mutations as a major cause of CHARGE association"],"prefix":"10.1002","volume":"111","author":[{"given":"Donna M.","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"Probst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon E.","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa 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