{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:13:28Z","timestamp":1791026008757,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003793","name":"Swedish Heart-Lung Foundation","doi-asserted-by":"publisher","award":["20180236"],"award-info":[{"award-number":["20180236"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2013-2546"],"award-info":[{"award-number":["2013-2546"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2012-2014"],"award-info":[{"award-number":["2012-2014"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut and Alice Wallenberg Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Fund for Neuromuscular Disorders"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function.<\/jats:p>","DOI":"10.1093\/hmg\/ddz032","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T15:15:28Z","timestamp":1548947728000},"page":"1919-1929","source":"Crossref","is-referenced-by-count":54,"title":["Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7141-4185","authenticated-orcid":false,"given":"Carola","family":"Hedberg-Oldfors","sequence":"first","affiliation":[{"name":"Department of Pathology and Genetics, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Abramsson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P S","family":"Osborn","sequence":"additional","affiliation":[{"name":"Genetics Research Centre, Molecular and Clinical Sciences Institute, St George\u2019s University of London, Cranmer Terrace, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof","family":"Danielsson","sequence":"additional","affiliation":[{"name":"Department of Neurology, and Department of Clinical and Experimental Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afsoon","family":"Fazlinezhad","sequence":"additional","affiliation":[{"name":"Razavi Cancer Research Center, Razavi Hospital, Imam Reza International University, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalda","family":"Nilipour","sequence":"additional","affiliation":[{"name":"Pediatric Pathology Research Center, Research Institute for Children Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"H\u00fcbbert","sequence":"additional","affiliation":[{"name":"Department of Medical and Health Sciences, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger","family":"Nennesmo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittichate","family":"Visuttijai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genetics, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaipreet","family":"Bharj","sequence":"additional","affiliation":[{"name":"Genetics Research Centre, Molecular and Clinical Sciences Institute, St George\u2019s University of London, Cranmer Terrace, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evmorfia","family":"Petropoulou","sequence":"additional","affiliation":[{"name":"Genetics Research Centre, Molecular and Clinical Sciences Institute, St George\u2019s University of London, Cranmer Terrace, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza","family":"Shoreim","sequence":"additional","affiliation":[{"name":"Genetics Research Centre, Molecular and Clinical Sciences Institute, St George\u2019s University of London, Cranmer Terrace, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Vona","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Julius Maximilians University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najmeh","family":"Ahangari","sequence":"additional","affiliation":[{"name":"Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela D\u00e1vila","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facilities, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Doosti","sequence":"additional","affiliation":[{"name":"Next Generation Genetic Polyclinic, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh Kumar","family":"Banote","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"Genetics Research Centre, Molecular and Clinical Sciences Institute, St George\u2019s University of London, Cranmer Terrace, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Edling","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Taherpour","sequence":"additional","affiliation":[{"name":"Razavi Cancer Research Center, Razavi Hospital, Imam Reza International University, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"},{"name":"Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan Ghayoor","family":"Karimiani","sequence":"additional","affiliation":[{"name":"Razavi Cancer Research Center, Razavi Hospital, Imam Reza International University, Mashhad, Iran"},{"name":"Innovative Medical Research Center, Faculty of Medicine, Mashhad Branch, Islamic Azad University, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Oldfors","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genetics, Institute of Biomedicine, University of Gothenburg, Gothenburg, 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Genet."},{"key":"2019102406291335400_ref5","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/ng.3701","article-title":"Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14 and human skin fragility","volume":"48","author":"Lin","year":"2016","journal-title":"Nat. Genet."},{"key":"2019102406291335400_ref6","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1002\/dvdy.22445","article-title":"Distinct troponin C isoform requirements in cardiac and skeletal muscle","volume":"239","author":"Sogah","year":"2010","journal-title":"Dev. Dyn."},{"key":"2019102406291335400_ref7","doi-asserted-by":"crossref","first-page":"e000231","DOI":"10.1161\/JAHA.113.000231","article-title":"Inactivation of Myosin binding protein C homolog in zebrafish as a model for human cardiac hypertrophy and diastolic dysfunction","volume":"2","author":"Chen","year":"2013","journal-title":"J. Am. Heart. 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Biophys. Res. Commun."},{"key":"2019102406291335400_ref16","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nature01985","article-title":"BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3","volume":"425","author":"Xu","year":"2003","journal-title":"Nature"},{"key":"2019102406291335400_ref17","doi-asserted-by":"crossref","first-page":"3730","DOI":"10.1172\/JCI93445","article-title":"Deficiency in Kelch protein Klhl31 causes congenital myopathy in mice","volume":"127","author":"Papizan","year":"2017","journal-title":"J. Clin. 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