{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T19:41:01Z","timestamp":1766086861020,"version":"3.37.3"},"reference-count":16,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T00:00:00Z","timestamp":1376611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Indiana University Health-Indiana University School of Medicine Strategic Research Initiative"},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["RO1NS058529"],"award-info":[{"award-number":["RO1NS058529"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000051","name":"NHGRI","doi-asserted-by":"crossref","award":["U54HG006542"],"award-info":[{"award-number":["U54HG006542"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Haploinsufficiency of <jats:italic>CHD7<\/jats:italic> (OMIM# 608892) is known to cause CHARGE syndrome (OMIM# 214800). Molecular testing supports a definitive diagnosis in approximately 65\u201370% of cases. Most <jats:italic>CHD7<\/jats:italic> mutations arise de novo, and no mutations affecting exon\u20107 have been reported to date. We report on an 8\u2010year\u2010old girl diagnosed with CHARGE syndrome that was referred to our laboratory for comprehensive <jats:italic>CHD7<\/jats:italic> gene screening. Genomic DNA from the subject with a suspected diagnosis of CHARGE was isolated from peripheral blood lymphocytes and comprehensive Sanger sequencing, along with deletion\/duplication analysis of the <jats:italic>CHD7<\/jats:italic> gene using multiplex ligation\u2010dependent probe amplification (MLPA), was performed. MLPA analysis identified a reduced single probe signal for exon\u20107 of the <jats:italic>CHD7<\/jats:italic> gene consistent with potential heterozygous deletion. Long\u2010range PCR breakpoint analysis identified a complex genomic rearrangement (CGR) leading to the deletion of exon\u20107 and breakpoints consistent with a replicative mechanism such as fork stalling and template switching (FoSTeS) or microhomology\u2010mediated break\u2010induced replication (MMBIR). Taken together this represents the first evidence for a <jats:italic>CHD7<\/jats:italic> intragenic CGR in a patient with CHARGE syndrome leading to what appears to be also the first report of a mutation specifically disrupting exon\u20107. Although likely rare, CGR may represent an overlooked mechanism in subjects with CHARGE syndrome that can be missed by current sequencing and dosage assays. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36178","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T17:32:59Z","timestamp":1376674379000},"page":"3182-3186","source":"Crossref","is-referenced-by-count":6,"title":["Evidence for replicative mechanism in a <i>CHD7<\/i> rearrangement in a patient with CHARGE syndrome"],"prefix":"10.1002","volume":"161","author":[{"given":"Matteo","family":"Vatta","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"},{"name":"Krannert Institute of Cardiology Indiana University School of Medicine Indianapolis Indiana"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyv","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"},{"name":"Department of Pediatrics Baylor College of Medicine Houston Texas"},{"name":"Texas Children's Hospital Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Putnam","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Hepatology and Nutrition Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine G.","family":"Spoonamore","sequence":"additional","affiliation":[{"name":"Krannert Institute of Cardiology Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine M.","family":"Eng","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alecia S.","family":"Willis","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston 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