{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:31:50Z","timestamp":1791048710949,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2007,11,13]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Brugada syndrome is a rare, autosomal-dominant, male-predominant form of idiopathic ventricular fibrillation characterized by a right bundle-branch block and ST elevation in the right precordial leads of the surface ECG. Mutations in the cardiac Na\n            <jats:sup>+<\/jats:sup>\n            channel SCN5A on chromosome 3p21 cause \u224820% of the cases of Brugada syndrome; most mutations decrease inward Na\n            <jats:sup>+<\/jats:sup>\n            current, some by preventing trafficking of the channels to the surface membrane. We previously used positional cloning to identify a new locus on chromosome 3p24 in a large family with Brugada syndrome and excluded\n            <jats:italic>SCN5A<\/jats:italic>\n            as a candidate gene.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We used direct sequencing to identify a mutation (A280V) in a conserved amino acid of the glycerol-3-phosphate dehydrogenase 1\u2013like (\n            <jats:italic>GPD1-L<\/jats:italic>\n            ) gene. The mutation was present in all affected individuals and absent in &gt;500 control subjects. GPD1-L RNA and protein are abundant in the heart. Compared with wild-type GPD1-L, coexpression of A280V GPD1-L with SCN5A in HEK cells reduced inward Na\n            <jats:sup>+<\/jats:sup>\n            currents by \u224850% (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.005). Wild-type GPD1-L localized near the cell surface to a greater extent than A280V GPD1-L. Coexpression of A280V GPD1-L with SCN5A reduced SCN5A cell surface expression by 31\u00b15% (\n            <jats:italic>P<\/jats:italic>\n            =0.01).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            <jats:italic>GPD1-L<\/jats:italic>\n            is a novel gene that may affect trafficking of the cardiac Na\n            <jats:sup>+<\/jats:sup>\n            channel to the cell surface. A GPD1-L mutation decreases SCN5A surface membrane expression, reduces inward Na\n            <jats:sup>+<\/jats:sup>\n            current, and causes Brugada syndrome.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.107.703330","type":"journal-article","created":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T23:19:55Z","timestamp":1193699995000},"page":"2260-2268","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":388,"title":["Mutation in Glycerol-3-Phosphate Dehydrogenase 1\u2013Like Gene (\n            <i>GPD1-L<\/i>\n            ) Decreases Cardiac Na\n            <sup>+<\/sup>\n            Current and Causes Inherited Arrhythmias"],"prefix":"10.1161","volume":"116","author":[{"given":"Barry","family":"London","sequence":"first","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Michalec","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haider","family":"Mehdi","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Kerchner","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamarendra","family":"Sanyal","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash C.","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold E.","family":"Pfahnl","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan L.","family":"Shang","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Madhusudanan","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine J.","family":"Baty","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Lagana","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Aleong","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Gutmann","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Ackerman","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis M.","family":"McNamara","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Weiss","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Samuel C.","family":"Dudley","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute (B.L., M. Michalec, H.M., X.Z., L.K., P.C.V., M. Madhusadanan, S.L., R.A., R.G., D.M.M.) and Department of Cell Biology and Physiology (B.L., P.C.V., C.J.B.), University of Pittsburgh, Pittsburgh Pa; Department of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, Ga (S.S., A.E.P., L.L.S., S.C.D.); Division of Cardiology, Mayo Clinic College of Medicine, Rochester, Minn (M.J.A.); and Division of Cardiology, Ohio State University, Columbus (R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000152479.54298.51"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.1997.tb00796.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(92)90253-J"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2005.50104.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/32675"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.20.2509"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2006.09.031"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.88.12.e78"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.104.25.3081"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.01.022"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.101.5.510"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.668392"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.100.15.1660"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.105.6.707"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.1073"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20011853"},{"key":"e_1_3_2_17_2","unstructured":"Myerburg RJ Castellanos A. Cardiac arrest and sudden cardiac death. In: Zipes DP Libby P Bonow RO Braunwald E eds. Braunwald\u2019s Heart Disease: A Textbook of Cardiovascular Medicine. 7th ed. Philadelphia Pa: Elsevier Saunders; 2005: 865\u2013904."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","unstructured":"Priori SG Rivolta I Napolitano C. Genetics of long QT Brugada and other channelopathies. In: Zipes DP Jalife J eds. Cardiac Electrophysiology: From Cell to Bedside. 4th ed. Philadelphia Pa: Saunders; 2004: 462\u2013470.","DOI":"10.1016\/B0-7216-0323-8\/50053-1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2005.50110.x"},{"key":"e_1_3_2_20_2","first-page":"634","volume":"21","year":"2003","unstructured":"Mohler PJ, Schott JJ, Gramolini AO, Dilly KW, Guatimosim S, duBell WH, Song LS, Haurogne K, Kyndt F, Ali ME, Rogers TB, Lederer WJ, Escande D, Le Marec H, Bennett V. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. 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