{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:46:20Z","timestamp":1789145180586,"version":"build-2803163510"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1995,3]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            Heart-hand syndromes compose a class of combined congenital cardiac and limb deformities. The prototypical heart-hand disorder is Holt-Oram syndrome, which is characterized by cardiac septation defects and radial ray limb deformity. We have recently mapped the Holt-Oram syndrome gene defect to the long arm of human chromosome 12 in two families. The role of this disease locus in the pathogenesis of related conditions such as heart-hand syndrome type III (cardiac conduction disease accompanied by skeletal malformations) or familial atrial septal defects is unknown.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            Clinical evaluations and genetic linkage analyses were performed in five additional kindreds with Holt-Oram syndrome and also in one kindred with heart-hand syndrome type III and one kindred with familial atrial septal defect and conduction disease. Holt-Oram syndrome in all five kindreds mapped to chromosome 12q2. These studies and previous data provide odds of greater than 10\n            <jats:sup>25<\/jats:sup>\n            :1 that the Holt-Oram syndrome disease gene is at chromosome 12q2. In contrast, neither the phenotypically similar disorder heart-hand syndrome type III nor the locus responsible for a familial atrial septal defect with atrioventricular block maps to chromosome 12q2.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            We demonstrate that heart-hand syndromes are genetically heterogeneous. Conditions that clinically appear to be partial phenocopies of Holt-Oram syndrome arise from distinct disease genes.\n          <\/jats:p>","DOI":"10.1161\/01.cir.91.5.1326","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:34:42Z","timestamp":1339461282000},"page":"1326-1329","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":53,"title":["Genetic Heterogeneity of Heart-Hand Syndromes"],"prefix":"10.1161","volume":"91","author":[{"given":"Craig T.","family":"Basson","sequence":"first","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Weissman","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calum A.","family":"MacRae","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew K.","family":"Poznanski","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Prieto","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador Ruiz","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Pease","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.E.","family":"Levin","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis B.","family":"Holmes","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.G.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine\u2013Cardiovascular Division (C.T.B., S.D.S., C.E.S.), Radiology (B.W.), and Howard Hughes Medical Institute (C.E.S.) at Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (C.A.M.) and Howard Hughes Medical Institute (J.G.S.) at Harvard Medical School, Boston, Mass; Department of Radiology (A.K.P.), Children\u2019s Memorial Hospital, Chicago, Ill; Unidad de Genetica (F.P., S.R.F.), Hospital Universitario \u201cLa Fe,\u201d Valencia, Spain; Division of Cardiology (W.E.P.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(75)90461-0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(83)80170-2"},{"key":"e_1_3_2_3_2","unstructured":"McKusick VA. 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