{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:46:08Z","timestamp":1790711168227,"version":"4.1.0"},"reference-count":34,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:p>\n                    CHARGE syndrome is an autosomal dominant multisystem disorder caused by mutation in the\n                    <jats:italic toggle=\"yes\">CHD7<\/jats:italic>\n                    gene, encoding chromodomain helicase DNA-binding protein 7. Molecular diagnostic testing for\n                    <jats:italic toggle=\"yes\">CHD7<\/jats:italic>\n                    mutation has been available in a clinical setting since 2005. We report here the results from the first 642 unrelated proband samples submitted for testing. Thirty-two percent (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u2009203) of patient samples had a heterozygous pathogenic variant identified. The lower mutation rate than that published for well-characterized clinical samples is likely due to referral bias, as samples submitted for clinical testing may be for \u201crule-out\u201d diagnoses, rather than solely to confirm clinical suspicion. We identified 159 unique pathogenic mutations, and of these, 134 mutations were each seen in a single individual and 25 mutations were found in two to five individuals (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200969). Of the 203 mutations, only 9 were missense, with 107 nonsense, 69 frameshift, and 15 splice-site mutations likely leading to haploinsufficiency at the cellular level. An additional 72 variations identified in the 642 tested samples (11%) were considered to have unknown clinical significance. Copy number changes (deletion\/duplication of the entire gene or one\/several exons) were found to account for a very small number of cases (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u20093). This cohort represents the largest CHARGE syndrome sample size to date and is intended to serve as a resource for clinicians, genetic counselors, researchers, and other diagnostic laboratories.\n                  <\/jats:p>","DOI":"10.1089\/gtmb.2010.0101","type":"journal-article","created":{"date-parts":[[2010,12,15]],"date-time":"2010-12-15T22:08:30Z","timestamp":1292450910000},"page":"881-891","source":"Crossref","is-referenced-by-count":47,"title":["Mutations in the\n                    <i>CHD7<\/i>\n                    Gene: The Experience of a Commercial Laboratory"],"prefix":"10.1177","volume":"14","author":[{"given":"Cynthia F.","family":"Bartels","sequence":"first","affiliation":[{"name":"Case Western Reserve University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Scacheri","sequence":"additional","affiliation":[{"name":"currently at Medco Health Solutions"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lashonda","family":"White","sequence":"additional","affiliation":[{"name":"GeneDx"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Scacheri","sequence":"additional","affiliation":[{"name":"Case Western Reserve University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherri","family":"Bale","sequence":"additional","affiliation":[{"name":"GeneDx"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2010,12,15]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00014395"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20330"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.10.044"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1419"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2008.03.003"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/000992289803700302"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00821.x"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100505"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01629"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31308"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1380"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03681.x"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810801918391"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30560"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.036061"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31921"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199912)60:6<334::AID-TERA5>3.0.CO;2-S"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/500273"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01127.x"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:VISI.0000029664.99615.94"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(81)80454-4"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01151.x"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkf493"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31816b5cae"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.036160"},{"key":"e_1_3_3_27_1","first-page":"6299","article-title":"Effect of 5\u2032 splice site mutations on splicing of the preceding intron","volume":"10","author":"Talerico M","year":"1990","unstructured":"Talerico M, , Berget SM. 1990. 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