{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:23:38Z","timestamp":1762161818009,"version":"3.28.0"},"reference-count":16,"publisher":"Texas Heart Institute Journal","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n        <jats:p>A 21-year-old man with sensorineural hearing loss and glaucoma presented with severely limited exercise capacity since childhood. He was found to have biventricular concentric hypertrophy with greatest wall thickening at the posterior and lateral walls of the left ventricle apex (1.7 cm) and the free wall of the right ventricle (1.1 cm). There was no inducible left ventricular outflow tract obstruction. Metabolic testing revealed marked lactic aciduria (1,650.1 \u03bcmol\/mmol creatinine) and plasma lactate (3.9 mmol\/L). A sarcomeric hypertrophic cardiomyopathy gene panel was unremarkable, but mitochondrial gene analysis revealed a homozygous c.385G&gt;A (p.Gly129Arg) pathogenic mutation in the <jats:italic>BCS1L<\/jats:italic> gene. This gene is responsible for an assembly subunit of cytochrome complex III in the respiratory transport chain and is the rarest respiratory chain defect. This gene has not frequently been implicated in cardiomyopathy. Mitochondrial hypertrophic cardiomyopathy is more rare than hypertrophic cardiomyopathy resulting from sarcomeric mutations and is more likely to be symmetric, less frequently results in left ventricular outflow tract obstruction, and is more likely to progress to dilated cardiomyopathy. Evidence-based screening protocols have not been established; treatment follows guideline-directed medical therapy for congestive heart failure, including evaluation for heart transplantation. This report expands the phenotype of the <jats:italic>BCS1L<\/jats:italic> mutation and suggests that affected patients may need screening for underlying cardiomyopathy.<\/jats:p>","DOI":"10.14503\/thij-21-7730","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T20:05:44Z","timestamp":1680293144000},"source":"Crossref","is-referenced-by-count":3,"title":["Pathogenic BCS1L Mutation Resulting in Hypertrophic Cardiomyopathy: A Unique Presentation of Nuclear Mitochondrial Disease"],"prefix":"10.14503","volume":"50","author":[{"given":"Cameron","family":"Incognito","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Hedley","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart & Vascular Institute, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine T.","family":"Posadas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangling","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Personalized Genetic Healthcare, Cleveland Clinic Community Care, Cleveland Clinic, Cleveland, Ohio"},{"name":"Department of Kidney Medicine, Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio"},{"name":"Molecular Medicine program, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milind","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart & Vascular Institute, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5628","reference":[{"issue":"3","key":"i1526-6702-50-2-e217730-b1","series-title":"Int J Cardiol.","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/j.ijcard.2014.11.014","article-title":"Cardiac manifestations of primary mitochondrial disorders","volume":"177","year":"2014","unstructured":"Finsterer\n              J,\n            \n            \n              Kothari\n              S.\n            \n          \n          Cardiac manifestations of primary mitochondrial disorders.\n\t\t\t\t\tInt J Cardiol.2014;177(3):754\u2013763.\n\t\t\t\t\tdoi:10.1016\/j.ijcard.2014.11.014"},{"issue":"9","key":"i1526-6702-50-2-e217730-b2","series-title":"Genet Med.","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/gim.2014.177","article-title":"Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society","volume":"17","year":"2015","unstructured":"Parikh\n              S,\n            \n            \n              Goldstein\n              A,\n            \n            \n              Koenig\n              MK,\n            \n          \n          .\n\t\t\t\t\tDiagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society.\n\t\t\t\t\tGenet Med.2015;17(9):689\u2013701.\n\t\t\t\t\tdoi:10.1038\/gim.2014.177"},{"issue":"5","key":"i1526-6702-50-2-e217730-b3","series-title":"Histopathology.","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1111\/j.1365-2559.2004.01835.x","article-title":"The pathology of hypertrophic cardiomyopathy","volume":"44","year":"2004","unstructured":"Hughes\n              SE.\n            \n          \n          The pathology of hypertrophic cardiomyopathy.\n\t\t\t\t\tHistopathology.2004;44(5):412\u2013427.\n\t\t\t\t\tdoi:10.1111\/j.1365-2559.2004.01835.x"},{"issue":"2","key":"i1526-6702-50-2-e217730-b4","series-title":"Card Electrophysiol Clin.","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.ccep.2015.03.008","article-title":"Mitochondrial cardiomyopathy and related arrhythmias","volume":"7","year":"2015","unstructured":"Montaigne\n              D,\n            \n            \n              Pentiah\n              AD.\n            \n          \n          Mitochondrial cardiomyopathy and related arrhythmias.\n\t\t\t\t\tCard Electrophysiol Clin.2015;7(2):293\u2013301.\n\t\t\t\t\tdoi:10.1016\/j.ccep.2015.03.008"},{"issue":"4","key":"i1526-6702-50-2-e217730-b5","series-title":"Tex Heart Inst J.","first-page":"385","article-title":"Mitochondrial cardiomyopathy: pathophysiology, diagnosis, and management","volume":"40","year":"2013","unstructured":"Meyers\n              DE,\n            \n            \n              Basha\n              HI,\n            \n            \n              Koenig\n              MK.\n            \n          \n          Mitochondrial cardiomyopathy: pathophysiology, diagnosis, and management.\n\t\t\t\t\tTex Heart Inst J.2013;40(4):385\u2013394."},{"issue":"7","key":"i1526-6702-50-2-e217730-b6","series-title":"Circ Res.","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1161\/CIRCRESAHA.117.311059","article-title":"Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy","volume":"121","year":"2017","unstructured":"Marian\n              AJ,\n            \n            \n              Braunwald\n              E.\n            \n          \n          Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy.\n\t\t\t\t\tCirc Res.2017;121(7):749\u2013770.\n\t\t\t\t\tdoi:10.1161\/CIRCRESAHA.117.311059"},{"issue":"4","key":"i1526-6702-50-2-e217730-b7","series-title":"J Mol Cell Cardiol.","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1006\/jmcc.2001.1340","article-title":"The molecular genetic basis for hypertrophic cardiomyopathy","volume":"33","year":"2001","unstructured":"Marian\n              AJ,\n            \n            \n              Roberts\n              R.\n            \n          \n          The molecular genetic basis for hypertrophic cardiomyopathy.\n\t\t\t\t\tJ Mol Cell Cardiol.2001;33(4):655\u2013670.\n\t\t\t\t\tdoi:10.1006\/jmcc.2001.1340"},{"issue":"1","key":"i1526-6702-50-2-e217730-b8","series-title":"Cardiovasc Ultrasound.","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12947-016-0072-5","article-title":"Echocardiographic diagnosis of the different phenotypes of hypertrophic cardiomyopathy","volume":"14","year":"2016","unstructured":"Parato\n              VM,\n            \n            \n              Antoncecchi\n              V,\n            \n            \n              Sozzi\n              F,\n            \n            ;\n\t\t\t\t\t\tItalian Chapter of ISCU.\n\t\t\t\t\t\n          Echocardiographic diagnosis of the different phenotypes of hypertrophic cardiomyopathy.\n\t\t\t\t\tCardiovasc Ultrasound.2016;14(1):30.\n\t\t\t\t\tdoi:10.1186\/s12947-016-0072-5"},{"issue":"11","key":"i1526-6702-50-2-e217730-b9","series-title":"J Am Coll Cardiol.","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.jacc.2010.05.007","article-title":"Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy","volume":"56","year":"2010","unstructured":"Bruder\n              O,\n            \n            \n              Wagner\n              A,\n            \n            \n              Jensen\n              CJ,\n            \n          \n          .\n\t\t\t\t\tMyocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy.\n\t\t\t\t\tJ Am Coll Cardiol.2010;56(11):875\u2013887.\n\t\t\t\t\tdoi:10.1016\/j.jacc.2010.05.007"},{"issue":"11","key":"i1526-6702-50-2-e217730-b10","series-title":"J Am Coll Cardiol.","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.jacc.2010.05.010","article-title":"Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy","volume":"56","year":"2010","unstructured":"O'Hanlon\n              R,\n            \n            \n              Grasso\n              A,\n            \n            \n              Roughton\n              M,\n            \n          \n          .\n\t\t\t\t\tPrognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy.\n\t\t\t\t\tJ Am Coll Cardiol.2010;56(11):867\u2013874.\n\t\t\t\t\tdoi:10.1016\/j.jacc.2010.05.010"},{"issue":"24","key":"i1526-6702-50-2-e217730-b11","series-title":"Eur Heart J.","doi-asserted-by":"publisher","first-page":"3023","DOI":"10.1093\/eurheartj\/ehs275","article-title":"Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management","volume":"33","year":"2012","unstructured":"Bates\n              MGD,\n            \n            \n              Bourke\n              JP,\n            \n            \n              Giordano\n              C,\n            \n            \n              d'Amati\n              G,\n            \n            \n              Turnbull\n              DM,\n            \n            \n              Taylor\n              RW.\n            \n          \n          Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management.\n\t\t\t\t\tEur Heart J.2012;33(24):3023\u20133033.\n\t\t\t\t\tdoi:10.1093\/eurheartj\/ehs275"},{"issue":"3","key":"i1526-6702-50-2-e217730-b12","series-title":"Am J Med Genet A.","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/ajmg.a.61019","article-title":"Clinical spectrum of BCS1L mitopathies and their underlying structural relationships","volume":"179","year":"2019","unstructured":"Baker\n              RA,\n            \n            \n              Priestley\n              JRC,\n            \n            \n              Wilstermann\n              AM,\n            \n            \n              Reese\n              KJ,\n            \n            \n              Mark\n              PR.\n            \n          \n          Clinical spectrum of BCS1L mitopathies and their underlying structural relationships.\n\t\t\t\t\tAm J Med Genet A.2019;179(3):373\u2013380.\n\t\t\t\t\tdoi:10.1002\/ajmg.a.61019"},{"issue":"5","key":"i1526-6702-50-2-e217730-b13","series-title":"J Inherit Metab Dis.","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1007\/s10545-012-9536-4","article-title":"Clinical and biochemical features associated with BCS1L mutation","volume":"36","year":"2013","unstructured":"Al-Owain\n              M,\n            \n            \n              Colak\n              D,\n            \n            \n              Albakheet\n              A,\n            \n          \n          .\n\t\t\t\t\tClinical and biochemical features associated with BCS1L mutation.\n\t\t\t\t\tJ Inherit Metab Dis.2013;36(5):813\u2013820.\n\t\t\t\t\tdoi:10.1007\/s10545-012-9536-4"},{"issue":"3","key":"i1526-6702-50-2-e217730-b14","series-title":"Tex Heart Inst J.","doi-asserted-by":"publisher","first-page":"e207243","DOI":"10.14503\/THIJ-20-7243","article-title":"Cardiovascular outcomes in patients with mitochondrial disease in the United States: a propensity score analysis","volume":"48","year":"2021","unstructured":"Nguyen\n              T,\n            \n            \n              Alzahrani\n              T,\n            \n            \n              Krepp\n              J,\n            \n            \n              Panjrath\n              G.\n            \n          \n          Cardiovascular outcomes in patients with mitochondrial disease in the United States: a propensity score analysis.\n\t\t\t\t\tTex Heart Inst J.2021;48(3):e207243.\n\t\t\t\t\tdoi:10.14503\/THIJ-20-7243"},{"issue":"2","key":"i1526-6702-50-2-e217730-b15","series-title":"Mol Genet Metab.","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.ymgme.2017.04.007","article-title":"Hospitalizations for mitochondrial disease across the lifespan in the U.S","volume":"121","year":"2017","unstructured":"McCormack\n              SE,\n            \n            \n              Xiao\n              R,\n            \n            \n              Kilbaugh\n              TJ,\n            \n          \n          .\n\t\t\t\t\tHospitalizations for mitochondrial disease across the lifespan in the U.S.\n\t\t\t\t\tMol Genet Metab.2017;121(2):119\u2013126.\n\t\t\t\t\tdoi:10.1016\/j.ymgme.2017.04.007"},{"issue":"4","key":"i1526-6702-50-2-e217730-b16","series-title":"Cochrane Database Syst Rev.","doi-asserted-by":"publisher","first-page":"CD004426","DOI":"10.1002\/14651858.CD004426.pub3","article-title":"Treatment for mitochondrial disorders","year":"2012","unstructured":"Pfeffer\n              G,\n            \n            \n              Majamaa\n              K,\n            \n            \n              Turnbull\n              DM,\n            \n            \n              Thorburn\n              D,\n            \n            \n              Chinnery\n              PF.\n            \n          \n          Treatment for mitochondrial disorders.\n\t\t\t\t\tCochrane Database Syst Rev.2012(4):CD004426.\n\t\t\t\t\tdoi:10.1002\/14651858.CD004426.pub3"}],"container-title":["Texas Heart Institute Journal"],"original-title":[],"link":[{"URL":"https:\/\/thij.kglmeridian.com\/view\/journals\/thij\/50\/2\/article-e217730.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/meridian.allenpress.com\/thij\/article-pdf\/doi\/10.14503\/THIJ-21-7730\/3413989\/i1526-6702-50-2-e217730.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thij.kglmeridian.com\/downloadpdf\/journals\/thij\/50\/2\/article-e217730.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thij.kglmeridian.com\/downloadpdf\/journals\/thij\/50\/2\/article-e217730.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T15:33:23Z","timestamp":1730993603000},"score":1,"resource":{"primary":{"URL":"https:\/\/thij.kglmeridian.com\/view\/journals\/thij\/50\/2\/article-e217730.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,1]]},"references-count":16,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.14503\/thij-21-7730","relation":{},"ISSN":["1526-6702","0730-2347"],"issn-type":[{"type":"electronic","value":"1526-6702"},{"type":"print","value":"0730-2347"}],"subject":[],"published":{"date-parts":[[2023,3,1]]}}}