Novel mutations in the sarcomeric protein myopalladin in patients with dilated cardiomyopathy

European Journal of Human Genetics : EJHG
Thomas MeyerGerman Competence Network Heart Failure

Abstract

Recently, missense mutations in titin-associated proteins have been linked to the pathogenesis of dilated cardiomyopathy (DCM). The objective of this study was to search for novel disease-associated mutations in the two human titin-binding proteins myopalladin and its amino-terminal-interacting partner cardiac ankyrin-repeat protein (CARP). In a cohort of 255 cases with familial and sporadic DCM, we analyzed the coding regions and all corresponding intron flanks located in the MYPN and CARP-encoding ANKRD1 gene. Two heterozygous missense mutations were detected in the MYPN gene (p.R955W and p.P961L), but neither of these mutations was found in 300 healthy controls. Both mutations were located in the α-actinin-binding region of myopalladin. Endomyocardial biopsies from the p.R955W carrier showed normal subcellular localization of myopalladin and α-actinin in cardiac myocytes, while their regular sarcomeric staining pattern was significantly disrupted in the p.P961L carrier, indicating that disturbed myofibrillogenesis and altered sarcomere assembly are the cause of the disease. In the ANKRD1 gene, we identified synonymous base exchanges (c.108T>C and c.-79C>T, respectively), but no non-synonymous mutations. In summary, we have i...Continue Reading

References

Dec 4, 2015·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Mehmet Enes CoşkunMehmet Yavuz Coşkun
May 29, 2015·Molecular Medicine Reports·Xin-Kai QuXing-Biao Qiu
Apr 18, 2015·Nature Reviews. Drug Discovery·Peter M Hwang, Brian D Sykes
Jun 23, 2016·European Journal of Human Genetics : EJHG·Eyal ReinsteinDoron M Behar
May 14, 2016·Journal of Cellular Physiology·Marie-Louise Bang
Feb 22, 2017·Annals of Neurology·Xavière LornageJocelyn Laporte
Oct 25, 2019·Journal of Cachexia, Sarcopenia and Muscle·Maria Carmela FilomenaMarie-Louise Bang
Feb 16, 2019·BMC Medical Genomics·Marwan M RefaatGeorges Nemer
Sep 7, 2019·International Journal of Molecular Sciences·Andreas BrodehlHendrik Milting

Citations

Feb 16, 2002·Biochemical and Biophysical Research Communications·Manatsu Itoh-SatohAkinori Kimura
Oct 22, 2003·Molecular Genetics and Metabolism·Bhagyalaxmi MohapatraNeil E Bowles
Dec 8, 2004·Journal of the American College of Cardiology·Takeharu HayashiAkinori Kimura
May 20, 2005·European Heart Journal·Karl SwedbergTask Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology
Sep 17, 2005·International Review of Cytology·Carol A OteyOlli Carpen
Jan 18, 2006·Heart Failure Reviews·Audrey N Chang, James D Potter
Feb 9, 2006·Journal of Muscle Research and Cell Motility·Yuji MatsumotoAkinori Kimura
Jun 7, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Wenxue LiangSaijuan Chen
Nov 17, 2007·Cardiovascular Research·Laëtitia Duboscq-BidotEric Villard
Jan 9, 2008·The Journal of Biological Chemistry·Richard DixonCarol A Otey
Mar 18, 2008·European Journal of Cell Biology·Silvia M GoicoecheaCarol A Otey
Oct 29, 2008·The International Journal of Developmental Biology·Alexander T Mikhailov, Mario Torrado
May 26, 2009·Cell Motility and the Cytoskeleton·Carol A OteySilvia M Goicoechea
Jun 16, 2009·European Heart Journal·Laëtitia Duboscq-BidotEUROGENE Heart Failure Network
Oct 19, 2010·Journal of the American College of Cardiology·Enkhsaikhan PurevjavJeffrey A Towbin
Apr 29, 2011·The New England Journal of Medicine·Hugh WatkinsCharles Redwood
Jul 14, 2011·European Journal of Heart Failure·Stephan WaldmüllerGerman Competence Network Heart Failure
Aug 4, 2011·European Heart Journal·Daniel Jacoby, William J McKenna
Dec 6, 2011·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·C ZugckS Störk
Jan 31, 2012·Human Molecular Genetics·Enkhsaikhan PurevjavJeffrey A Towbin
Feb 18, 2012·The New England Journal of Medicine·Daniel S HermanChristine E Seidman

Related Concepts

Establishment and Maintenance of Localization
Cardiomyopathy, Familial Idiopathic
Pathogenic Aspects
Carp antigen
Sarcomeres
Pathogenesis
Carp, fish
Immunoglobulin Domain
ANKRD1 protein, human
Ankyrins

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.