The arrhythmogenic cardiomyopathy phenotype associated with PKP2 c.1211dup variant

被引：3

作者：

Bos, Thomas A. ^{[1
]}

Piers, Sebastiaan R. D. ^{[2
]}

Wessels, Marja W. ^{[3
]}

Houweling, Arjan C. ^{[4
]}

Bokenkamp, Regina ^{[5
]}

Bootsma, Marianne ^{[2
]}

Bosman, Laurens P. ^{[6
]}

Evertz, Reinder ^{[7
]}

Hellebrekers, Debby M. E. I. ^{[8
]}

Hoedemaekers, Yvonne M. ^{[9
]}

Knijnenburg, Jeroen ^{[1
]}

Deprez, Ronald Lekanne ^{[4
]}

van Mil, Anneke M. ^{[1
]}

te Riele, Anneline S. J. M. ^{[6
,10
]}

van Slegtenhorst, Marjon A. ^{[3
]}

Wilde, Arthur A. M. ^{[11
]}

Yap, Sing-Chien ^{[12
]}

Dooijes, Dennis ^{[13
]}

Koopmann, Tamara T. ^{[1
]}

van Tintelen, J. Peter ^{[6
,13
]}

Barge-Schaapveld, Daniela Q. C. M. ^{[1
]}

机构：

[1] Leiden Univ, Dept Clin Genet, Med Ctr, Leiden, Netherlands

[2] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands

[3] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

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

[5] Leiden Univ, Dept Paediat Cardiol, Med Ctr, Leiden, Netherlands

[6] Netherlands ACM Registry, Utrecht, Netherlands

[7] Radboud Univ Nijmegen, Dept Cardiol, Med Ctr, Nijmegen, Netherlands

[8] Maastricht Univ, Dept Clin Genet, Med Ctr, Maastricht, Netherlands

[9] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Nijmegen, Netherlands

[10] Univ Med Ctr Utrecht, Div Cardiol, Dept Heart & Lungs, Utrecht, Netherlands

[11] Amsterdam Uni Med Ctr, Ctr Heart, Heart Failure & Arrhythmias, Amsterdam Cardiovasc Sci,Dept Cardiol, Amsterdam, Netherlands

[12] Erasmus MC, Dept Cardiol, Rotterdam, Netherlands

[13] Univ Med Ctr Utrecht, Dept Clin Genet, Utrecht, Netherlands

来源：

NETHERLANDS HEART JOURNAL | 2023年 / 31卷 / 7-8期

关键词：

Arrhythmogenic Cardiomyopathy; Plakophilin-2; Founder mutation; Genetics; PLAKOPHILIN-2; MUTATIONS; CLINICAL PRESENTATION; OUTCOMES;

D O I：

10.1007/s12471-023-01791-2

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundThe arrhythmogenic cardiomyopathy (ACM) phenotype, with life-threatening ventricular arrhythmias and heart failure, varies according to genetic aetiology. We aimed to characterise the phenotype associated with the variant c.1211dup (p.Val406Serfs*4) in the plakophilin-2 gene (PKP2) and compare it with previously reported Dutch PKP2 founder variants.MethodsClinical data were collected retrospectively from medical records of 106 PKP2 c.1211dup heterozygous carriers. Using data from the Netherlands ACM Registry, c.1211dup was compared with 3 other truncating PKP2 variants (c.235C > T (p.Arg79*), c.397C > T (p.Gln133*) and c.2489+1G > A (p.?)).ResultsOf the 106 carriers, 47 (44%) were diagnosed with ACM, at a mean age of 41 years. By the end of follow-up, 29 (27%) had experienced sustained ventricular arrhythmias and 12 (11%) had developed heart failure, with male carriers showing significantly higher risks than females on these endpoints (p < 0.05). Based on available cardiac magnetic resonance imaging and echocardiographic data, 46% of the carriers showed either right ventricular dilatation and/or dysfunction, whereas a substantial minority (37%) had some form of left ventricular involvement. Both geographical distribution of carriers and haplotype analysis suggested PKP2 c.1211dup to be a founder variant originating from the South-Western coast of the Netherlands. Finally, a Cox proportional hazards model suggested significant differences in ventricular arrhythmia-free survival between 4 PKP2 founder variants, including c.1211dup.ConclusionsThe PKP2 c.1211dup variant is a Dutch founder variant associated with a typical right-dominant ACM phenotype, but also left ventricular involvement, and a possibly more severe phenotype than other Dutch PKP2 founder variants.

引用

页码：315 / 323

页数：9

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