{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:52:32Z","timestamp":1791035552822,"version":"4.1.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2000,7,25]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    \u2014Cytogenetic evidence suggests that the haploinsufficiency of \u22651 gene located in 8p23 behaves as a dominant mutation, impairing heart differentiation and leading to a wide spectrum of congenital heart defects (CHDs), including conotruncal lesions, atrial septal defects, atrioventricular canal defects, and pulmonary valve stenosis. An 8p heart-defect\u2013critical region was delineated, and the zinc finger transcription factor GATA4 was considered a likely candidate for these defects. We narrowed this region and excluded a major role of GATA4 in these CHDs.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Methods and Results<\/jats:italic>\n                    \u2014We studied 12 patients (7 had CHD and 5 did not) with distal 8p deletions from 9 families by defining their chromosome rearrangements at the molecular level by fluorescent in situ hybridization and short-tandem repeat analysis. Subjects with 8p deletions distal to D8S1706, at \u224810 cM from the 8p telomere, did not have CHD, whereas subjects with a deletion that included the more proximal region suffered from the spectrum of heart defects reported in patients with 8p distal deletions. The 5-cM critical region is flanked distally by D8S1706 and WI-8327, both at \u224810 cM, and proximally by D8S1825, at 15 cM. Neither GATA4 nor angiopoietin-2 (ANGPT2; a gene in 8p23 involved in blood vessel formation) were found to be deleted in some of the critical patients. We also found that CHDs are not related to the parental origin of deletion.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusions<\/jats:italic>\n                    \u2014Haploinsufficiency for a gene between WI-8327 and D8S1825 is critical for heart development. A causal relationship does not seem to exist between GATA4 and ANGPT2 haploinsufficiency and CHDs.\n                  <\/jats:p>","DOI":"10.1161\/01.cir.102.4.432","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T20:42:29Z","timestamp":1339447349000},"page":"432-437","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Deletion of a 5-cM Region at Chromosome 8p23 Is Associated With a Spectrum of Congenital Heart Defects"],"prefix":"10.1161","volume":"102","author":[{"given":"Sabrina","family":"Giglio","sequence":"first","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Graw","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Gimelli","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Pirola","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Varone","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucille","family":"Voullaire","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Lerzo","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Rossi","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Dellavecchia","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Clara","family":"Bonaglia","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Digilio","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Giannotti","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Marino","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romeo","family":"Carrozzo","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie R.","family":"Korenberg","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Danesino","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Sujansky","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Dallapiccola","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. Medea, Bosisio Parini, Lecco, Italy (M.C.B); the Genetica Medica e Cardiologia,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsetta","family":"Zuffardi","sequence":"additional","affiliation":[{"name":"From the Biologia Generale e Genetica Medica, Universita\u0300 di Pavia, Pavia, Italy (S.G., B.P., E.R., C. Dellavecchia, C. Danesino, O.Z.); the Eleanor Roosevelt Institute, Denver, Co (S.L.G.); the Laboratorio di Citogenetica and Divisione di Cardiochirurgia, Istituto G. Gaslini, Genova, Italy (G.G., P.V., F.L.); the Murdoch Institute, Royal Children\u2019s Hospital, Parkville, Australia (L.V.); the Istituto Scientifico E. 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