{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T21:27:18Z","timestamp":1770067638224,"version":"3.49.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2006,6,13]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Mutations in sarcomere protein,\n            <jats:italic>PRKAG2<\/jats:italic>\n            ,\n            <jats:italic>LAMP2<\/jats:italic>\n            , \u03b1-galactosidase A (\n            <jats:italic>GLA<\/jats:italic>\n            ), and several mitochondrial genes can cause rare familial cardiomyopathies, but their contribution to increased left ventricular wall thickness (LVWT) in the community is unknown.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We studied 1862 unrelated participants (52% women; age, 59\u00b19 years) from the community-based Framingham Heart Study who had echocardiograms and provided DNA samples but did not have severe hypertension, aortic prosthesis, or significant aortic stenosis. Eight sarcomere protein genes, 3 storage cardiomyopathy\u2013causing genes, and 27 mitochondrial genes were sequenced in unrelated individuals with increased LVWT (maximum LVWT &gt;13 mm). Fifty eligible participants (9 women) had unexplained increased LVWT. We detected 8 mutations in 9 individuals (2 women); 7 mutations in 5 sarcomere protein genes (\n            <jats:italic>MYH7, MYBPC3, TNNT2, TNNI3, MYL3<\/jats:italic>\n            ), and 1\n            <jats:italic>GLA<\/jats:italic>\n            mutation. In individuals with increased LVWT, participants with sarcomere protein and storage mutations were clinically indistinguishable from those without mutations.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            In a community-based cohort, about 3% of eligible participants had increased LVWT, of whom 18% had sarcomere protein or lipid storage gene mutations. Increased LVWT in the community is a very heterogeneous condition, which sometimes may arise from single-gene variants in one of a number of genes.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.105.593558","type":"journal-article","created":{"date-parts":[[2006,6,6]],"date-time":"2006-06-06T00:58:15Z","timestamp":1149555495000},"page":"2697-2705","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":111,"title":["Single-Gene Mutations and Increased Left Ventricular Wall Thickness in the Community"],"prefix":"10.1161","volume":"113","author":[{"given":"Hiroyuki","family":"Morita","sequence":"first","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin G.","family":"Larson","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott C.","family":"Barr","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramachandran S.","family":"Vasan","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel N.","family":"Hirschhorn","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Levy","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Corey","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.G.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emelia J.","family":"Benjamin","sequence":"additional","affiliation":[{"name":"From The Program in Genomics Applications: CardioGenomics Group\u2014the Department of Genetics (H.M., S.B., C.E.S., J.G.S.), Massachusetts General Hospital (C.J.O.), and Children\u2019s Hospital (J.N.H.), Harvard Medical School; Boston University School of Medicine, Boston (M.G.L., R.S.V., D.L., E.J.B.); the National Heart, Lung, and Blood Institute\u2019s Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., C.J.O., D.L., D.C., E.J.B.); and Massachusetts Institute of Technology, Cambridge, Mass (J.N.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2001.113218"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000165625.79933.9a"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200402000-00011"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.5.1416"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-004-0009-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00242-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.6.080604.162132"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.10.1308"},{"key":"e_1_3_2_9_2","unstructured":"Benjamin EJ Hirschhorn J Izumo S Seidman JG. CardioGenomics Project Website. The Program in Genomics Applications Cardiogenomics Project. 2005. http:\/\/cardiogenomics.med.harvard.edu. Accessed May 22 2006."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033349"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.92.4.785"},{"key":"e_1_3_2_12_2","unstructured":"Celera Discovery System. 2005. http:\/\/www.celeradiscoverysystem.com\/."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.07.045"},{"key":"e_1_3_2_14_2","unstructured":"Ingman M. mtDB-Human Mitochondrial Genome Database. 2005. http:\/\/www.genpat.uu.se\/mtDB\/mainframe.html. Accessed May 22 2006."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4065\/80.4.463"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000066323.15244.54"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.105.4.446"},{"key":"e_1_3_2_18_2","first-page":"1186","volume":"53","year":"1993","unstructured":"Eng CM, Resnick-Silverman LA, Niehaus DJ, Astrin KH, Desnick RJ. Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease. Am J Hum Genet. 1993; 53: 1186\u20131197.","journal-title":"Am J Hum Genet"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000012626.81324.38"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990219)82:5<436::AID-AJMG14>3.0.CO;2-X"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199508033330504"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000091253.71282.04"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198903233201201"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199804303381802"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001573-200205000-00006"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.105.593558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T04:27:45Z","timestamp":1715574465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.105.593558"}},"subtitle":["The Framingham Heart Study"],"short-title":[],"issued":{"date-parts":[[2006,6,13]]},"references-count":25,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2006,6,13]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.105.593558"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.105.593558","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,6,13]]},"assertion":[{"value":"2006-06-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}