A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients

被引：5

作者：

Nagyova, Emilia ^{[1
,2
]}

Hoorntje, Edgar T. ^{[3
,4
]}

te Rijdt, Wouter P. ^{[3
,4
]}

Bosman, Laurens P. ^{[1
]}

Syrris, Petros ^{[5
]}

Protonotarios, Alexandros ^{[5
,6
]}

Elliott, Perry M. ^{[5
]}

Tsatsopoulou, Adalena ^{[6
]}

Mestroni, Luisa ^{[7
]}

Taylor, Matthew R. G. ^{[7
]}

Sinagra, Gianfranco ^{[8
]}

Merlo, Marco ^{[8
]}

Wada, Yuko ^{[9
,10
]}

Horie, Minoru ^{[10
]}

Mogensen, Jens ^{[11
]}

Christensen, Alex H. ^{[12
,13
]}

Gerull, Brenda ^{[14
,15
,16
]}

Song, Lei ^{[17
,18
]}

Yao, Yan ^{[17
,18
]}

Fan, Siyang ^{[17
,18
]}

Saguner, Ardan M. ^{[19
]}

Duru, Firat ^{[19
]}

Koskenvuo, Juha W. ^{[20
]}

Marino, Tania Cruz ^{[21
]}

Tichnell, Crystal ^{[22
]}

Judge, Daniel P. ^{[23
]}

Dooijes, Dennis ^{[24
]}

Deprez, Ronald Lekanne H. ^{[25
]}

Basso, Cristina ^{[26
]}

Pilichou, Kalliopi ^{[26
]}

Bauce, Barbara ^{[26
]}

Wilde, Arthur A. M. ^{[27
]}

Charron, Philippe ^{[28
]}

Fressart, Veronique ^{[28
]}

van der Heijden, Jeroen F. ^{[1
]}

van den Berg, Maarten P. ^{[29
]}

Asselbergs, Folkert W. ^{[1
,30
,31
,32
]}

James, Cynthia A. ^{[22
]}

Jongbloed, Jan D. H. ^{[3
]}

Harakalova, Magdalena ^{[1
,4
,33
]}

van Tintelen, J. Peter ^{[4
,24
,25
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands

[2] Comenius Univ, Fac Nat Sci, Dept Mol Biol, Bratislava, Slovakia

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[4] Netherlands Heart Inst, Utrecht, Netherlands

[5] UCL, Inst Cardiovasc Sci, Ctr Heart Muscle Dis, London, England

[6] Nikos Protonotarios Med Ctr, Naxos 84300, Greece

[7] Univ Colorado, Cardiovasc Inst, Anschutz Med Campus, Aurora, CO USA

[8] Azienda Sanitaria Univ Giuliano Isontina ASUGI, Cardiothoracovasc Dept, Trieste, Italy

[9] Vanderbilt Univ, Dept Med, Med Ctr, Nashville, TN USA

[10] Shiga Univ Med Sci, Dept Cardiovasc Med, Otsu, Japan

[11] Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark

[12] Dept Cardiol, Herlev Gentofte, Denmark

[13] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark

[14] Libin Cardiovasc Inst Alberta, Dept Cardiac Sci, Calgary, AB, Canada

[15] Univ Hosp Wurzburg, Comprehens Heart Failure Ctr CHFC, Wurzburg, Germany

[16] Univ Hosp Wurzburg, Dept Internal Med 1, Wurzburg, Germany

[17] Peking Union Med Coll Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Arrhythmia Ctr, Beijing, Peoples R China

[18] Peking Union Med Coll Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Clin EP Lab,State Key Lab Cardiovasc Dis, Beijing, Peoples R China

[19] Univ Heart Ctr, Dept Cardiol, Zurich, Switzerland

[20] Blueprint Genet, Helsinki, Finland

[21] CIUSSS Saguenay Lac St Jean, Dept Med Biol, Chicoutimi, PQ, Canada

[22] Johns Hopkins Univ, Dept Med, Div Cardiol, Sch Med, Baltimore, MD USA

[23] Med Univ South Carolina, Dept Med, Div Cardiol, Charleston, SC USA

[24] Univ Utrecht, Univ Med Ctr Utrecht, Dept Genet, Utrecht, Netherlands

[25] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Human Genet, Amsterdam, Netherlands

[26] Univ Padua, Dept Cardiac Thorac Vasc Sci & Publ Hlth, Padua, Italy

[27] Univ Amsterdam, Amsterdam Univ Med Ctr, Heart Ctr, Dept Clin & Expt Cardiol, Amsterdam, Netherlands

[28] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, Referral Ctr Cardiac Hereditary Dis, Paris, France

[29] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[30] UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England

[31] UCL, Hlth Data Res UK, London, England

[32] UCL, Inst Hlth Informat, London, England

[33] Univ Utrecht, Univ Med Ctr Utrecht, Regenerat Med Utrecht RMU, Utrecht, Netherlands

来源：

JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH | 2023年 / 16卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

ARVC; Multiple variants; Desmosomal genes; Composite endpoint; Arrhythmia; Genetics; MUTATION; RISK; DIAGNOSIS; COMPOUND;

D O I：

10.1007/s12265-023-10403-8

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy.

引用

页码：1276 / 1286

页数：11

共 50 条

[1] A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients
Emilia Nagyova
Edgar T. Hoorntje
Wouter P. te Rijdt
Laurens P. Bosman
Petros Syrris
Alexandros Protonotarios
Perry M. Elliott
Adalena Tsatsopoulou
Luisa Mestroni
Matthew R. G. Taylor
Gianfranco Sinagra
Marco Merlo
Yuko Wada
Minoru Horie
Jens Mogensen
Alex H. Christensen
Brenda Gerull
Lei Song
Yan Yao
Siyang Fan
Ardan M. Saguner
Firat Duru
Juha W. Koskenvuo
Tania Cruz Marino
Crystal Tichnell
Daniel P. Judge
Dennis Dooijes
Ronald H. Lekanne Deprez
Cristina Basso
Kalliopi Pilichou
Barbara Bauce
Arthur A. M. Wilde
Philippe Charron
Véronique Fressart
Jeroen F. van der Heijden
Maarten P. van den Berg
Folkert W. Asselbergs
Cynthia A. James
Jan D. H. Jongbloed
Magdalena Harakalova
J. Peter van Tintelen
Journal of Cardiovascular Translational Research, 2023, 16 : 1276 - 1286
[2] Desmosomal gene evaluation in Boxers with arrhythmogenic right ventricular cardiomyopathy
Meurs, Kathryn M.
Ederer, Martina M.
Stern, Joshua A.
AMERICAN JOURNAL OF VETERINARY RESEARCH, 2007, 68 (12) : 1338 - 1341
[3] Clinical profile of patients affected by dominant desmosomal arrhythmogenic right ventricular cardiomyopathy
Tsatsopoulou, A.
Antoniades, L.
Anastasakis, A.
Syrris, P.
Asimaki, A.
Daniel, G.
Vouliotis, A.
Stefanadis, C.
Protonotarios, N.
EUROPEAN HEART JOURNAL, 2009, 30 : 288 - 288
[4] Comprehensive analysis of desmosomal gene mutations in Han Chinese patients with arrhythmogenic right ventricular cardiomyopathy
Zhou, Xiujuan
Chen, Minglong
Song, Hualian
Wang, Benqi
Chen, Hongwu
Wang, Jing
Wang, Wei
Feng, Shangpeng
Zhang, Fengxiang
Ju, Weizhu
Li, Mingfang
Gu, Kai
Cao, Kejiang
Wang, Dao W.
Yang, Bing
EUROPEAN JOURNAL OF MEDICAL GENETICS, 2015, 58 (04) : 258 - 265
[5] Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations
Bauce, Barbara
Rampazzo, Alessandra
Basso, Cristina
Mazzotti, Elisa
Rigato, Ilaria
Steriotis, Alexandros
Beffagna, Giorgia
Lorenzon, Alessandra
De Bortoli, Marzia
Pilichou, Kalliopi
Marra, Martina Perazzolo
Corbetti, Francesco
Daliento, Luciano
Iliceto, Sabino
Corrado, Domenico
Thiene, Gaetano
Nava, Andrea
HEART RHYTHM, 2011, 8 (11) : 1686 - 1695
[6] Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice
Fressart, Veronique
Duthoit, Guillaume
Donal, Erwan
Probst, Vincent
Deharo, Jean-Claude
Chevalier, Philippe
Klug, Didier
Dubourg, Olivier
Delacretaz, Etienne
Cosnay, Pierre
Scanu, Patrice
Extramiana, Fabrice
Keller, Dagmar
Hidden-Lucet, Francoise
Simon, Francoise
Bessirard, Vanessa
Roux-Buisson, Nathalie
Hebert, Jean-Louis
Azarine, Arshid
Casset-Senon, Daniele
Rouzet, Francois
Lecarpentier, Yves
Fontaine, Guy
Coirault, Catherine
Frank, Robert
Hainque, Bernard
Charron, Philippe
EUROPACE, 2010, 12 (06): : 861 - 868
[7] Arrhythmogenic right ventricular cardiomyopathy: analysis of a paediatric population carrying desmosomal gene mutations
Rigato, I.
Rampazzo, A.
Basso, C.
Mazzotti, E.
Corbetti, F.
Daliento, L.
Corrado, D.
Iliceto, S.
Nava, A.
Bauce, B.
EUROPEAN HEART JOURNAL, 2010, 31 : 188 - 189
[8] Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2
Syrris, Petros
Ward, Deirdre
Evans, Alison
Asimaki, Angeliki
Gandjbakhch, Estelle
Sen-Chowdhry, Srijita
McKenna, William J.
AMERICAN JOURNAL OF HUMAN GENETICS, 2006, 79 (05) : 978 - 984
[9] Clinical Impact of Desmosomal and Titin Gene Mutations on the Natural History of Arrhythmogenic Right Ventricular Cardiomyopathy
Brun, Francesca
Barnes, Carl
Sinagra, Gianfranco
Slavov, Dobromir
Barbati, Giulia
Zhu, Xiao
Begay, Rene
Graw, Sharon
Pinamonti, Bruno
Salcedo, Ernesto E.
Taylor, Matthew
Mestroni, Luisa
CIRCULATION, 2013, 128 (22)
[10] Sports in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy and desmosomal mutations
Sawant, A. C.
Calkins, H.
HERZ, 2015, 40 (03) : 402 - 409

← 1 2 3 4 5 →