{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:50:12Z","timestamp":1793235012728,"version":"4.5.0"},"reference-count":24,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>Homozygous deletions\/mutations of the <jats:italic>SMN1<\/jats:italic> gene cause infantile spinal muscular atrophy (SMA). The presence of at least one <jats:italic>SMN2<\/jats:italic> gene copy is required for normal embryogenesis. Lack of SMN protein results in degeneration of motor neurons, while extraneuronal manifestations have been regarded as a chance association with SMA. We report on heart defects in the subgroup of congenital SMA type I patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>Data were recruited from 65 unselected SMA I patients whose diagnosis had been confirmed genetically within the first 6 months of age. <jats:italic>SMN2<\/jats:italic> copy numbers were analysed retrospectively and correlated with clinical findings including heart malformations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Four (6%) patients had one copy of <jats:italic>SMN2<\/jats:italic>, 56 (86%) had two and five (8%) had three <jats:italic>SMN2<\/jats:italic> copies. Three out of four (75%) patients with a single <jats:italic>SMN2<\/jats:italic> copy had congenital SMA with haemodynamically relevant atrial or ventricular septal defects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Previous case reports of SMA I patients with congenital heart defects did not clarify whether the cardiac malformations were coincidental. Given the respective incidences of congenitally lethal SMA with a single <jats:italic>SMN2<\/jats:italic> copy and of cardiac septal defects in humans, a chance association of both conditions would occur in less than one out of 50 million individuals. Our findings suggest that the SMN protein is relevant for normal cardiogenesis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.057950","type":"journal-article","created":{"date-parts":[[2008,7,28]],"date-time":"2008-07-28T20:43:47Z","timestamp":1217277827000},"page":"635-638","source":"Crossref","is-referenced-by-count":187,"title":["Congenital heart disease is a feature of severe infantile spinal muscular atrophy"],"prefix":"10.1136","volume":"45","author":[{"given":"S","family":"Rudnik-Sch\u00f6neborn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Heller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Betzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Grimm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Eggermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Eggermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Wirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Wirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Zerres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2008,7,28]]},"reference":[{"key":"2025101710454379000_45.10.635.1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1399-0004.1990.tb03553.x","article-title":"Spinal muscular atrophy type I combined with atrial septal defects in three sibs.","volume":"38","author":"Moller","year":"1990","journal-title":"Clin Genet"},{"key":"2025101710454379000_45.10.635.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2005.07.005"},{"key":"2025101710454379000_45.10.635.3","doi-asserted-by":"publisher","DOI":"10.1086\/338627"},{"key":"2025101710454379000_45.10.635.4","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-006-0051-3"},{"key":"2025101710454379000_45.10.635.5","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0828-x"},{"key":"2025101710454379000_45.10.635.6","first-page":"161","article-title":"Modifikation des Ph\u00e4notyps der proximalen spinalen Muskelatrophie (SMA) durch die SMN2-Genkopie.","volume":"17","author":"Zerres","year":"2005","journal-title":"Medgen"},{"key":"2025101710454379000_45.10.635.7","doi-asserted-by":"publisher","DOI":"10.1080\/14767050500433817"},{"key":"2025101710454379000_45.10.635.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92206-7"},{"key":"2025101710454379000_45.10.635.9","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-973741"},{"key":"2025101710454379000_45.10.635.10","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400509"},{"key":"2025101710454379000_45.10.635.11","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1055\/s-2007-973805","article-title":"Spinal muscular atrophy combined with congenital heart disease: a report of two cases.","volume":"27","author":"Mulleners","year":"1996","journal-title":"Neuropediatr"},{"key":"2025101710454379000_45.10.635.12","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1212\/WNL.51.3.878","article-title":"Large-scale deletions in a Chinese infant associated with a variant form of Werdnig-Hoffmann disease.","volume":"51","author":"Jong","year":"1998","journal-title":"Neurology"},{"key":"2025101710454379000_45.10.635.13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1090-3798(99)80015-4","article-title":"Prenatal onset spinal muscular atrophy.","volume":"3","author":"Macleod","year":"1999","journal-title":"Eur J Paediatr Neurol"},{"key":"2025101710454379000_45.10.635.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-004-1437-6"},{"key":"2025101710454379000_45.10.635.15","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0825-3"},{"key":"2025101710454379000_45.10.635.16","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951105002131"},{"key":"2025101710454379000_45.10.635.17","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807299954"},{"key":"2025101710454379000_45.10.635.18","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/ajmg.a.32233","article-title":"Congenital heart defects in spinal muscular atrophy type I. a clinical report of two siblings and a review of the literature.","volume":"146A","author":"Menke","year":"2008","journal-title":"Am J Med Genet"},{"key":"2025101710454379000_45.10.635.19","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.16.2451"},{"key":"2025101710454379000_45.10.635.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2004.08.024"},{"key":"2025101710454379000_45.10.635.21","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.5.849"},{"key":"2025101710454379000_45.10.635.22","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.152.5.1107"},{"key":"2025101710454379000_45.10.635.23","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/S0002-9440(10)63428-1","article-title":"Deletion of murine exon 7 directed to the liver leads to severe defect of liver development associated with iron overload.","volume":"165","author":"Vitte","year":"2004","journal-title":"Am J Pathol"},{"key":"2025101710454379000_45.10.635.24","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199903)45:3<337::AID-ANA9>3.0.CO;2-U"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.2008.057950","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:45:52Z","timestamp":1760723152000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.2008.057950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,28]]},"references-count":24,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2008,10,3]]},"published-print":{"date-parts":[[2008,10]]}},"alternative-id":["10.1136\/jmg.2008.057950"],"URL":"https:\/\/doi.org\/10.1136\/jmg.2008.057950","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7,28]]}}}