{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:33:36Z","timestamp":1787495616285,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T00:00:00Z","timestamp":1361318400000},"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":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Disease causing mutations for heterotaxy syndrome were first identified in the X\u2010linked laterality gene,\n                    <jats:italic>ZIC3<\/jats:italic>\n                    . Mutations typically result in males with\n                    <jats:italic>situs ambiguus<\/jats:italic>\n                    and complex congenital heart disease; however affected females and one male with isolated d\u2010transposition of the great arteries (d\u2010TGA) have been reported. We hypothesized that a subset of patients with heart defects common to heterotaxy but without laterality defects would have\n                    <jats:italic>ZIC3<\/jats:italic>\n                    mutations. We also sought to estimate the prevalence of\n                    <jats:italic>ZIC3<\/jats:italic>\n                    mutations in sporadic heterotaxy. Patients with TGA (n\u2009=\u2009169), double outlet right ventricle (DORV; n\u2009=\u200989), common atrioventricular canal (CAVC; n\u2009=\u200941), and heterotaxy (n\u2009=\u200954) underwent sequencing of\n                    <jats:italic>ZIC3<\/jats:italic>\n                    exons. We tested 90 patients with tetralogy of Fallot (TOF) to correlate genotype with phenotype. Three potentially disease\u2010related missense mutations were detected: c.49G\u2009&gt;\u2009T (Gly17Cys) in a female with isolated DORV, c.98C\u2009&gt;\u2009T (Ala33Val) in a male with isolated d\u2010TGA, and c.841C\u2009&gt;\u2009T (His281Tyr) in a female with sporadic heterotaxy. We also identified a novel insertion (CPFP333ins) in a family with heterotaxy. All were absent in 200 control patients and the 1000 Genomes Project (n\u2009=\u2009629). No significant mutations were found in patients with TOF. Functional studies demonstrated reduced transcriptional activity of the ZIC3 His281Tyr mutant protein.\n                    <jats:italic>ZIC3<\/jats:italic>\n                    mutations were rarely identified in isolated DORV and d\u2010TGA suggesting that a subset of DORV and d\u2010TGA may fall within the spectrum of laterality defects.\n                    <jats:italic>ZIC3<\/jats:italic>\n                    mutations were found in 3.7% of patients with sporadic heterotaxy; therefore testing should be considered in patients with heterotaxy. \u00a9 2013 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.35849","type":"journal-article","created":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T17:26:57Z","timestamp":1361381217000},"page":"792-802","source":"Crossref","is-referenced-by-count":43,"title":["The phenotypic spectrum of\n                    <i>ZIC3<\/i>\n                    mutations includes isolated d\u2010transposition of the great arteries and double outlet right ventricle"],"prefix":"10.1002","volume":"161","author":[{"given":"Lisa C.A.","family":"D'Alessandro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brande C.","family":"Latney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasuna C.","family":"Paluru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Goldmuntz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.87.2.146"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20480"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ppedcard.2006.01.006"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.3577405"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747\u20100803.2011.00602.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2009.181685"},{"key":"e_1_2_6_9_1","unstructured":"Exome Variant Server NHLBI GO Exome Sequencing Project (ESP) Seattle WA.URL: http:\/\/evs.gs.washington.edu\/EVS\/[date accessed: August 2012]."},{"key":"e_1_2_6_10_1","volume-title":"Genetic and environmental risk factors of major cardiovascular malformations","author":"Ferencz C","year":"1997"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti486"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-305"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00812-3"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)00062-X"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200005000-00002"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200526"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.176601"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.212802"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.9.2293"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.308"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","unstructured":"SiepelA PollardKS HausslerD.2006.New methods for detecting lineage\u2010specific selection. 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