Human Molecular Genetics, 2015, Vol. 24, No. 25 7227–7240 doi: 10.1093/hmg/ddv423 Advance Access Publication Date: 12 October 2015 Original Article ORIGINAL ARTICLE PLEKHM2 mutation leads to abnormal localization Downloaded from of lysosomes, impaired autophagy flux and associates with recessive dilated cardiomyopathy and left ventricular noncompaction http://hmg.oxfordjournals.org/ Emad Muhammad1,†, Aviva Levitas2,†, Sonia R. Singh3,4, Alex Braiman1, Rivka Ofir5, Sharon Etzion5, Val C. Sheffield6, Yoram Etzion5,7, Lucie Carrier3,4 and Ruti Parvari1,8,* 1Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel, 2Department of Pediatric Cardiology, Soroka University Medical Center and at Bibliothekssystem Universitaet Hamburg on December 2, 2015 Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel, 3Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany, 4DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany, 5Regenerative Medicine and Stem Cell Research Center, Beer-Sheva 84105, Israel, 6Department of Pediatrics, Division of Medical Genetics and Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA, 7Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel and 8National Institute for Biotechnology in the Negev, Ben- Gurion University of the Negev, Beer-Sheva, Israel *To whom correspondence should be addressed. Tel: +972 86479967; Fax: +972 86472983; Email:
[email protected] Abstract Gene mutations, mostly segregating with a dominant mode of inheritance, are important causes of dilated cardiomyopathy (DCM), a disease characterized by enlarged ventricular dimensions, impaired cardiac function, heart failure and high risk of death.