Personalized Medicine Approach in a DCM Patient with

familial DCM individualized therapy lamin mutation laminopathy mTOR inhibitor

Journal

Journal of personalized medicine
ISSN: 2075-4426
Titre abrégé: J Pers Med
Pays: Switzerland
ID NLM: 101602269

Informations de publication

Date de publication:
15 Jul 2022
Historique:
received: 22 06 2022
revised: 10 07 2022
accepted: 13 07 2022
entrez: 27 7 2022
pubmed: 28 7 2022
medline: 28 7 2022
Statut: epublish

Résumé

Mutations in the We report a 47-year-old DCM patient with severely impaired left ventricular ejection fraction and NYHA functional class IV despite optimal heart failure treatment. Whole-exome sequencing revealed an LMNA E161K missense mutation as the pathogenetic cause for DCM in this patient. We generated a patient-specific Beta adrenergic stimulation of cardiomyocytes derived from We have successfully generated the first in vitro model to recapitulate a patient-specific LMNA E161K mutation which leads to a severe form of DCM. The model may serve as a template for individualized and specific treatment of heart failure.

Sections du résumé

BACKGROUND BACKGROUND
Mutations in the
METHODS METHODS
We report a 47-year-old DCM patient with severely impaired left ventricular ejection fraction and NYHA functional class IV despite optimal heart failure treatment. Whole-exome sequencing revealed an LMNA E161K missense mutation as the pathogenetic cause for DCM in this patient. We generated a patient-specific
RESULTS RESULTS
Beta adrenergic stimulation of cardiomyocytes derived from
CONCLUSION CONCLUSIONS
We have successfully generated the first in vitro model to recapitulate a patient-specific LMNA E161K mutation which leads to a severe form of DCM. The model may serve as a template for individualized and specific treatment of heart failure.

Identifiants

pubmed: 35887646
pii: jpm12071149
doi: 10.3390/jpm12071149
pmc: PMC9323361
pii:
doi:

Types de publication

Journal Article

Langues

eng

Références

Curr Protoc Stem Cell Biol. 2010 Dec;Chapter 1:Unit 1F.11
pubmed: 21125557
J Mol Cell Cardiol. 2009 Sep;47(3):352-8
pubmed: 19406126
PLoS One. 2010 Dec 14;5(12):e14342
pubmed: 21179469
Biotechnol Lett. 2011 Apr;33(4):853-8
pubmed: 21165673
Mol Ther Nucleic Acids. 2020 Sep 4;21:696-711
pubmed: 32769060
Lancet. 2017 Jul 22;390(10092):400-414
pubmed: 28190577
Sci Transl Med. 2012 Jul 25;4(144):144ra102
pubmed: 22837537
Front Cell Dev Biol. 2021 Jan 28;9:638542
pubmed: 33585493
Curr Treat Options Cardiovasc Med. 2017 Mar;19(3):21
pubmed: 28299614
J Am Heart Assoc. 2019 Jun 4;8(11):e012514
pubmed: 31433726
Dev Dyn. 2016 Feb;245(2):157-65
pubmed: 26515123
Biomed Res Int. 2015;2015:163564
pubmed: 26504781
Nat Rev Genet. 2006 Dec;7(12):940-52
pubmed: 17139325
Int J Cardiol. 2018 Dec 15;273:168-176
pubmed: 30279005
Circ Res. 2002 Aug 9;91(3):189-201
pubmed: 12169644
Curr Cardiol Rep. 2018 Sep 27;20(11):121
pubmed: 30259183
Biol Cell. 2014 Oct;106(10):346-58
pubmed: 25055884
Curr Opin Cardiol. 2013 May;28(3):297-304
pubmed: 23455585
J Vis Exp. 2008 Jul 23;(17):
pubmed: 19066514
J Vis Exp. 2014 Sep 23;(91):52010
pubmed: 25286293
Cells. 2020 Aug 11;9(8):
pubmed: 32796718
Per Med. 2018 Mar;15(2):127-136
pubmed: 29714129
Int J Mol Sci. 2021 Jul 23;22(15):
pubmed: 34360639
Cell Rep. 2016 Dec 6;17(10):2542-2552
pubmed: 27926859
Methods Mol Biol. 2011;690:151-62
pubmed: 21042991
J Am Coll Cardiol. 2005 Apr 5;45(7):969-81
pubmed: 15808750
Heart. 2018 Mar;104(6):468-479
pubmed: 29175975
Nature. 2019 Aug;572(7769):335-340
pubmed: 31316208
J Clin Endocrinol Metab. 2007 Dec;92(12):4835-44
pubmed: 17711925
Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):10100-10105
pubmed: 30224463

Auteurs

Balram Neupane (B)

Department of Cardiology, Angiology and Critical Care (Medical Clinic 1), University Hospital RWTH Aachen, 52074 Aachen, Germany.

Kabita Pradhan (K)

Department of Cardiology, Angiology and Critical Care (Medical Clinic 1), University Hospital RWTH Aachen, 52074 Aachen, Germany.

Audrey Magdalena Ortega-Ramirez (AM)

Institute of Physiology, RWTH Aachen University, 52074 Aachen, Germany.

Parwez Aidery (P)

Department of Cardiology and Angiology, University Hospital of Tübingen, 72076 Tübingen, Germany.

Vytautas Kucikas (V)

Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany.

Matthias Marks (M)

Clinic for Neurology, Section Neurobiological Research, University Hospital RWTH Aachen, 52074 Aachen, Germany.
Interdisciplinary Centre for Clinical Research (IZKF) Aachen, Transgenic Service, University Hospital RWTH Aachen, 52074 Aachen, Germany.

Marc A M J van Zandvoort (MAMJ)

Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany.
Cardiovascular Research Institute Maastricht (CARIM), Department of Molecular Cell Biology, Maastricht University, 6229 ER Maastricht, The Netherlands.

Karin Klingel (K)

Cardiopathology, Institute for Pathology, University Hospital of Tübingen, 72076 Tübingen, Germany.

Klaus K Witte (KK)

Department of Cardiology, Angiology and Critical Care (Medical Clinic 1), University Hospital RWTH Aachen, 52074 Aachen, Germany.

Stefan Gründer (S)

Institute of Physiology, RWTH Aachen University, 52074 Aachen, Germany.

Nikolaus Marx (N)

Department of Cardiology, Angiology and Critical Care (Medical Clinic 1), University Hospital RWTH Aachen, 52074 Aachen, Germany.

Michael Gramlich (M)

Department of Cardiology, Angiology and Critical Care (Medical Clinic 1), University Hospital RWTH Aachen, 52074 Aachen, Germany.

Classifications MeSH