{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:48:13Z","timestamp":1792280893274,"version":"4.4.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2000,11,10]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Heterozygous mutations in the cardiac homeobox gene,\n            <jats:italic>NKX2-5<\/jats:italic>\n            , underlie familial cases of atrial septal defect (ASD) with severe atrioventricular conduction block. In this study, mice heterozygous for\n            <jats:italic>Nkx2-5<\/jats:italic>\n            \u2013null alleles were assessed for analogous defects. Although ASD occurred only rarely, atrial septal dysmorphogenesis was evident as increased frequencies of patent foramen ovale and septal aneurysm, and decreased length of the septum primum flap valve. These parameters were compounded by genetic background effects, and in the 129\/Sv strain, septal dysmorphogenesis bordered on ASD in 17% of\n            <jats:italic>Nkx2-5<\/jats:italic>\n            heterozygotes. In a proportion of neonatal heterozygotes, as well as in adults with ASD, we found that the size of the foramen ovale was significantly enlarged and altered in shape, potentially exposing the normally thin septum primum to excessive hemodynamic forces. Therefore, defective morphogenesis of the septum secundum may be one contributing factor in the generation of patent foramen ovale, septal aneurysm, and certain ASDs. Mild prolongation of P-R interval in females and an increased frequency of stenotic bicuspid aortic valves were also features of the\n            <jats:italic>Nkx2-5<\/jats:italic>\n            heterozygous phenotype. Our data demonstrate that the complex effects of\n            <jats:italic>Nkx2-5<\/jats:italic>\n            haploinsufficiency in mice are weaker but convergent with those in humans. As in the mouse, the phenotype of human\n            <jats:italic>NKX2-5<\/jats:italic>\n            mutations may be modulated by interacting alleles.\n          <\/jats:p>","DOI":"10.1161\/01.res.87.10.888","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:52:16Z","timestamp":1339462336000},"page":"888-895","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":293,"title":["Cardiac Septal and Valvular Dysmorphogenesis in Mice Heterozygous for Mutations in the Homeobox Gene\n            <i>Nkx2-5<\/i>"],"prefix":"10.1161","volume":"87","author":[{"given":"Christine","family":"Biben","sequence":"first","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Weber","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Kesteven","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard","family":"Stanley","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lachlan","family":"McDonald","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Elliott","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Barnett","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ko\u0308entgen","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Robb","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Feneley","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Harvey","sequence":"additional","affiliation":[{"name":"From the Victor Chang Cardiac Research Institute (C.B., S.K., L.M., D.A.E., M.F., R.P.H.), Darlinghurst, Australia; Walter and Eliza Hall Institute of Medical Research (R.W., E.S., L.B., F.K., L.R.), Royal Melbourne Hospital, Parkville, Australia; Cardiology Department (S.K., M.F.), St Vincent\u2019s Hospital, St Darlinghurst, Australia; and Faculties of Medicine and Life Sciences (R.P.H.), University of New South Wales, Kensington, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","unstructured":"Freed MD Plauth WH Jr. The pathology pathophysiology recognition and treatment of congenital heart disease. 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