{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:52:26Z","timestamp":1790693546606,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Spontaneous coronary artery dissection (SCAD) is an uncommon idiopathic disorder predominantly affecting young, otherwise healthy women. Rare familial cases reveal a genetic predisposition to disease. The aim of this study was to identify a novel susceptibility gene for SCAD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Whole-exome sequencing was performed in a family comprised of 3 affected individuals and filtered to identify rare, predicted deleterious, segregating variants. Immunohistochemical staining was used to evaluate protein expression of the identified candidate gene. The prevalence and spectrum of rare (&lt;0.1%) variants within binding domains was determined by next-generation sequencing or denaturing high-performance liquid chromatography in a sporadic SCAD cohort of 675 unrelated individuals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              We identified a rare heterozygous missense variant within a highly conserved \u03b2-integrin\u2013binding domain of\n              <jats:italic>TLN1<\/jats:italic>\n              segregating with familial SCAD.\n              <jats:italic>TLN1<\/jats:italic>\n              encodes talin 1\u2014a large cytoplasmic protein of the integrin adhesion complex that links the actin cytoskeleton and extracellular matrix. Consistent with high mRNA expression in arterial tissues, robust immunohistochemical staining of talin 1 was demonstrated in coronary arteries. Nine additional rare heterozygous missense variants in\n              <jats:italic>TLN1<\/jats:italic>\n              were identified in 10 sporadic cases. Incomplete penetrance, suggesting genetic or environmental modifiers of this episodic disorder, was evident in the familial case and 5 individuals with sporadic SCAD from whom parental DNA was available.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Our findings reveal\n              <jats:italic>TLN1<\/jats:italic>\n              as a disease-associated gene in familial and sporadic SCAD and, together with abnormal vascular phenotypes reported in animal models of talin 1 disruption, implicate impaired structural integrity of the coronary artery cytoskeleton in SCAD susceptibility.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.118.002437","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T18:00:11Z","timestamp":1555437611000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":58,"title":["Rare Missense Variants in\n            <i>TLN1<\/i>\n            Are Associated With Familial and Sporadic Spontaneous Coronary Artery Dissection"],"prefix":"10.1161","volume":"12","author":[{"given":"Tamiel N.","family":"Turley","sequence":"first","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Department of Molecular Pharmacology and Experimental Therapeutics (T.N.T.), Mayo Clinic, Rochester, MN."},{"name":"Cardiovascular Genetics Research Laboratory (T.N.T., J.L.T., R.S.S., T.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne L.","family":"Theis","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Research Laboratory (T.N.T., J.L.T., R.S.S., T.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhianna S.","family":"Sundsbak","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Research Laboratory (T.N.T., J.L.T., R.S.S., T.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (J.M.E., M.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M.","family":"O\u2019Byrne","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (J.M.E., M.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Gulati","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (R.G., M.S.T., S.N.H., T.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marysia S.","family":"Tweet","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (R.G., M.S.T., S.N.H., T.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharonne N.","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (R.G., M.S.T., S.N.H., T.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Olson","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Research Laboratory (T.N.T., J.L.T., R.S.S., T.M.O.), Mayo Clinic, Rochester, MN."},{"name":"Department of Cardiovascular Medicine (R.G., M.S.T., S.N.H., T.M.O.), Mayo Clinic, Rochester, MN."},{"name":"Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine (T.M.O.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000564"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.105718"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2014.8307"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.07.040"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2015.3824"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.114.001676"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1262110"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-009-0009-4"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.018085"},{"key":"e_1_3_4_11_2","first-page":"1907","article-title":"The tale of two talins \u2013 two isoforms to fine-tune signaling.","volume":"12","author":"Gough RE","year":"2018","unstructured":"Gough, RE, et al. 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