A Novel DSP Truncating Variant in a Family with Episodic Myocardial Injury in the Course of Arrhythmogenic Cardiomyopathy-A Possible Role of a Low Penetrance NLRP3 Variant

Diagnostics
Przemysław ChmielewskiZofia T Bilińska

Abstract

Mono-allelic dominant mutations in the desmoplakin gene (DSP) have been linked to known cardiac disorders, such as arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy. During the course of DSP cardiomyopathy, episodes of acute myocardial injury may occur. While their mechanisms remain unclear, myocarditis has been postulated as an underlying cause. We report on an adolescent girl with arrhythmogenic biventricular cardiomyopathy and three acute myocarditis-like episodes in whom we found a novel truncating DSP variant accompanied by a known low penetrance R490K variant in the NLRP3. Upon family screening, other carriers of the DSP variant have been identified in whom only mild cardiac abnormalities were found. We hypothesized that the uncommon course of cardiomyopathy in the proband as well as striking discrepancies in the phenotype observed in her family may be explained by the co-existence of her low penetrance genetic autoinflammatory predisposition.

References

Sep 17, 1998·Journal of the American Academy of Dermatology·L Carvajal-Huerta
Mar 19, 2002·Journal of the American College of Cardiology·Eloisa ArbustiniLuigi Tavazzi
Jan 13, 2006·Nature·Thirumala-Devi KannegantiGabriel Núñez
Jan 13, 2006·Nature·Sanjeev MariathasanVishva M Dixit
Oct 24, 2006·Annals of the New York Academy of Sciences·Thomas A KuferDana J Philpott
Apr 15, 2009·The Journal of Experimental Medicine·Helen J LachmannThomas Jung
Jun 5, 2010·Cell and Tissue Research·Rita M CabralAndrew P South
Aug 19, 2010·Circulation. Cardiovascular Genetics·Perry ElliottWilliam J McKenna
Jul 7, 2012·Journal of the American College of Cardiology·Gabriel LaurentVincent Probst
Jan 18, 2014·Circulation Research·Rafal PloskiZofia T Bilinska
Apr 30, 2014·Clinical and Experimental Immunology·M H HaverkampS M Holland
May 27, 2014·Cell·Mohamed Lamkanfi, Vishva M Dixit
Jan 18, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Nikolaus RieberJasmin Kuemmerle-Deschner
Oct 5, 2016·Polskie Archiwum Medycyny Wewnętrznej·Bogna Foss-NieradkoZofia T Bilińska
Dec 3, 2016·Journal of the American College of Cardiology·Martín F Ortiz-GengaLorenzo Monserrat
May 12, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Keith NykampScott Topper
Jul 12, 2017·Arthritis & Rheumatology·J B Kuemmerle-DeschnerS M Benseler
Apr 12, 2019·Clinical Immunology : the Official Journal of the Clinical Immunology Society·E SchuhT Kümpfel
Jun 19, 2019·European Journal of Heart Failure·Perry M ElliottJ Peter van Tintelen
Sep 20, 2019·Circulation·Stephen P ChelkoJeffrey E Saffitz
Apr 18, 2020·ESC Heart Failure·Antheia KissopoulouCecilia Gunnarsson
May 16, 2020·Journal of Clinical Medicine·Przemyslaw ChmielewskiZofia T Bilinska
May 16, 2020·Journal of the American Heart Association·Wolfgang PollerSabine Klaassen
Jun 21, 2020·International Journal of Cardiology·Domenico CorradoCristina Basso

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Citations

Aug 4, 2021·Chinese Medical Journal·Zhong-Yu YuanYong-Quan Wu

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Methods Mentioned

BETA
exome sequencing
biopsy

Software Mentioned

Variant Reporter
Annovar
Integrative Genomics Viewer ( IGV

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