{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:12:49Z","timestamp":1792663969132,"version":"4.5.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>The genetic variation underlying many heritable forms of cardiovascular disease is incompletely understood, even in patients with strong family history or early age at onset.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We used whole exome sequencing to detect pathogenic variants in 55 patients with suspected monogenic forms of cardiovascular disease. Diagnostic analysis of established disease genes identified pathogenic variants in 21.8% of cases and variants of uncertain significance in 34.5% of cases. Three patients harbored heterozygous nonsense or splice-site variants in the nucleoporin genes\n              <jats:italic>NUP37<\/jats:italic>\n              ,\n              <jats:italic>NUP43<\/jats:italic>\n              , and\n              <jats:italic>NUP188<\/jats:italic>\n              , which have not been implicated previously in cardiac disease. We also identified a heterozygous splice site variant in the nuclear envelope gene\n              <jats:italic>SYNE1<\/jats:italic>\n              in a child with severe dilated cardiomyopathy that underwent transplant, as well as in his affected father. To confirm a cardiovascular role for these candidate genes in vivo, we used morpholinos to reduce\n              <jats:italic>SYNE1, NUP37,<\/jats:italic>\n              and\n              <jats:italic>NUP43<\/jats:italic>\n              gene expression in zebrafish. Morphant embryos displayed cardiac abnormalities, including pericardial edema and heart failure. Furthermore, lymphoblasts from the patient carrying a\n              <jats:italic>SYNE1<\/jats:italic>\n              splice-site variant displayed changes in nuclear morphology and protein localization that are consistent with disruption of the nuclear envelope.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              These data expand the repertoire of pathogenic variants associated with cardiovascular disease and validate the diagnostic and research use of whole exome sequencing. We identify\n              <jats:italic>NUP37<\/jats:italic>\n              ,\n              <jats:italic>NUP43<\/jats:italic>\n              , and\n              <jats:italic>NUP188<\/jats:italic>\n              as novel candidate genes for cardiovascular disease, and suggest that dysfunction of the nuclear envelope may be an under-recognized component of inherited cardiac disease in some cases.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.116.001443","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T01:10:27Z","timestamp":1497402627000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Whole Exome Sequencing Identifies Truncating Variants in Nuclear Envelope Genes in Patients With Cardiovascular Disease"],"prefix":"10.1161","volume":"10","author":[{"given":"Gloria T.","family":"Haskell","sequence":"first","affiliation":[{"name":"From the Department of Pathology, Duke University, Durham, NC (G.T.H.); Division of Cardiology (B.C.J.), McAllister Heart Institute (B.C.J., L.A.S., W.H., J.L.), Department of Cell and Molecular Physiology (L.A.S., W.H., J.L.), Department of Genetics (D.M., C.S., C.T., B.A.S., E.A.R.-M., B.K., K.C.W., K.E.W., J.P.E., J.S.B.), Department of Pathology and Laboratory Medicine (J.L., K.E.W.), UNC School of Medicine, Chapel Hill; Renaissance Computing Institute, Chapel Hill, NC (K.C.W.); and ECU Heart..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Jensen","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Duke University, Durham, NC (G.T.H.); Division of Cardiology (B.C.J.), McAllister Heart Institute (B.C.J., L.A.S., W.H., J.L.), Department of Cell and Molecular Physiology (L.A.S., W.H., J.L.), Department of Genetics (D.M., C.S., C.T., B.A.S., E.A.R.-M., B.K., K.C.W., K.E.W., J.P.E., J.S.B.), Department of Pathology and Laboratory Medicine (J.L., K.E.W.), UNC School of Medicine, Chapel Hill; Renaissance Computing Institute, Chapel Hill, NC (K.C.W.); and ECU Heart..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh Ann","family":"Samsa","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Duke University, Durham, NC (G.T.H.); Division of Cardiology (B.C.J.), McAllister Heart Institute (B.C.J., L.A.S., W.H., J.L.), Department of Cell and Molecular Physiology (L.A.S., W.H., J.L.), Department of Genetics (D.M., C.S., C.T., B.A.S., E.A.R.-M., B.K., K.C.W., K.E.W., J.P.E., J.S.B.), Department of Pathology and Laboratory Medicine (J.L., K.E.W.), UNC School of Medicine, Chapel Hill; Renaissance Computing Institute, Chapel Hill, NC (K.C.W.); and ECU Heart..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Marchuk","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Duke University, Durham, NC (G.T.H.); Division of Cardiology (B.C.J.), McAllister Heart Institute (B.C.J., L.A.S., W.H., J.L.), Department of Cell and Molecular Physiology (L.A.S., W.H., J.L.), Department of Genetics (D.M., C.S., C.T., B.A.S., E.A.R.-M., B.K., K.C.W., K.E.W., J.P.E., J.S.B.), Department of Pathology and Laboratory Medicine (J.L., K.E.W.), UNC School of Medicine, Chapel Hill; Renaissance Computing Institute, Chapel Hill, NC (K.C.W.); and ECU Heart..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Duke University, Durham, NC (G.T.H.); Division of Cardiology (B.C.J.), McAllister Heart Institute (B.C.J., L.A.S., W.H., J.L.), Department of Cell and Molecular Physiology (L.A.S., W.H., J.L.), Department of Genetics (D.M., C.S., C.T., B.A.S., E.A.R.-M., B.K., K.C.W., K.E.W., J.P.E., J.S.B.), Department of Pathology and Laboratory Medicine (J.L., K.E.W.), UNC School of Medicine, Chapel Hill; Renaissance Computing Institute, Chapel Hill, NC (K.C.W.); and ECU Heart..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecile","family":"Skrzynia","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Duke University, Durham, NC (G.T.H.); Division of Cardiology (B.C.J.), McAllister Heart Institute (B.C.J., L.A.S., W.H., J.L.), Department of Cell and Molecular Physiology (L.A.S., W.H., J.L.), Department of Genetics (D.M., C.S., C.T., B.A.S., E.A.R.-M., B.K., K.C.W., K.E.W., J.P.E., J.S.B.), Department of Pathology and Laboratory Medicine (J.L., K.E.W.), UNC School of Medicine, Chapel Hill; 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