{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:16:07Z","timestamp":1782299767355,"version":"3.54.5"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2005,11]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Nonobstructive hypertrophy localized to the cardiac apex is an uncommon morphological variant of hypertrophic cardiomyopathy (HCM) that often is further distinguished by distinct giant negative T waves and a benign clinical course. The genetic relationship between HCM with typical hypertrophic morphology versus isolated apical hypertrophy is incompletely understood.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Genetic cause was investigated in 15 probands with apical hypertrophy by DNA sequence analyses of 9 sarcomere protein genes and 3 other genes (\n            <jats:italic>GLA<\/jats:italic>\n            ,\n            <jats:italic>PRKAG2<\/jats:italic>\n            , and\n            <jats:italic>LAMP2<\/jats:italic>\n            ) implicated in idiopathic cardiac hypertrophy. Six sarcomere gene mutations were found in 7 samples; no samples contained mutations in\n            <jats:italic>GLA<\/jats:italic>\n            ,\n            <jats:italic>PRKAG2<\/jats:italic>\n            , or\n            <jats:italic>LAMP2<\/jats:italic>\n            . Clinical evaluations demonstrated familial apical HCM in 4 probands, and in 3 probands disease-causing mutations were identified. Two families shared a cardiac actin Glu101Lys missense mutation; all members of both families with clinical manifestations of HCM (n=16) had apical hypertrophy. An essential light chain missense mutation Met149Val caused apical or midventricular segment HCM in another proband and 5 family members, but 6 other affected relatives had typical HCM morphologies. No other sarcomere gene mutations identified in the remaining probands caused apical HCM in other family members.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Sarcomere protein gene mutations that cause apical hypertrophy rather than more common HCM morphologies reflect interactions among genetic etiology, background modifier genes, and\/or hemodynamic factors. Only a limited number of sarcomere gene defects (eg, cardiac actin Glu101Lys) consistently produce apical HCM.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.105.547448","type":"journal-article","created":{"date-parts":[[2005,11,2]],"date-time":"2005-11-02T21:38:28Z","timestamp":1130967508000},"page":"2805-2811","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":168,"title":["Gene Mutations in Apical Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"112","author":[{"given":"Michael","family":"Arad","sequence":"first","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manual","family":"Penas-Lado","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Monserrat","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Maron","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sherrid","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn Y.","family":"Ho","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Barr","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Karim","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Olson","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsohiro","family":"Kamisago","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.G.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, Mass (M.A., S.B., M.K., J.G.S., C.E.S.); Heart Institute, Sheba Medical Center, Tel Hashomer, Israel (M.A.); Cardiology Service, Hospital Juan Canalejo, La Corun\u0303a, Spain (M.P.-L., L.M.); Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.); St Luke\u2019s Roosevelt University Hospital, New York, NY (M.S.); Division of Cardiology and Howard Hughes Medical Institute, Brigham and Women\u2019s Hospital, Boston, Mass (C.Y.H., C.E.S.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2003.07.027"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.62.728.567"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.17.611"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(79)90388-6"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(95)00377-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(95)00390-8"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-106-5-663"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.92.9.2488"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(82)90200-4"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001573-199505000-00011"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0897-379"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.6.663"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.98.5.391"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.12.3069"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.05.088"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(88)91233-7"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/clc.4950250207"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2000.1204"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0596-63"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00242-2"},{"key":"e_1_3_3_21_2","unstructured":"Seidman C DePalma SR McDonough B Seidman JG. 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