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. 2022 Apr 27;13(5):782.
doi: 10.3390/genes13050782.

New Variant in Placophilin-2 Gene Causing Arrhythmogenic Myocardiopathy

Fiama Caimi-Martinez  1 , Guido Antoniutti  1 , Rocio Blanco  1 , Bernardo García de la Villa  2 , Nelson Alvarenga  3 , Nancy Govea-Callizo  4   5 , Laura Torres-Juan  4 , Damián Heine-Suñer  4   5 , Jordi Rosell-Andreo  4   5 , David Crémer Luengos  1 , Jorge Alvarez-Rubio  1   5 , Tomás Ripoll-Vera  1   5   6
Affiliations

New Variant in Placophilin-2 Gene Causing Arrhythmogenic Myocardiopathy

Fiama Caimi-Martinez et al. Genes (Basel). .

Abstract

Introduction: Arrhythmogenic cardiomyopathy (ACM) is an inherited disease characterized by progressive fibroadipose replacement of cardiomyocytes. Its diagnosis is based on imaging, electrocardiographic, histological and genetic/familial criteria. The development of the disease is based mainly on desmosomal genes. Knowledge of the phenotypic expression of each of these genes will help in both diagnosis and prognosis. The objective of this study is to describe the genotype-phenotype association of an unknown PKP2 gene variant in a family diagnosed with ACM.

Methods: Clinical and genetic study of a big family carrying the p.Tyr168* variant in the PKP2 gene, in order to demonstrate pathogenicity of this variant, causing ACM.

Results: Twenty-two patients (proband and relatives) were evaluated. This variant presented with high arrhythmic load at an early age, but without evidence of structural heart disease after 20 years of follow-up, with low risk in predictive scores. We demonstrate evidence of its pathogenicity.

Conclusions: The p.Tyr168* variant in the PKP2 gene causes ACM with a high arrhythmic load and with an absence of structural heart disease. This fact emphasizes the value of knowing the phenotypic expression of each variant.

Keywords: CVD genetics; NGS for diagnostics of CVDs-; cardiomyopathies.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Arrhythmogenic cardiomyopathy sudden death risk calculator. Adapted from ARVC risk. N°: number, PVCs: premature ventricular complex, H: hours, VT: Ventricular tachycardia.
Figure 2
Figure 2
Family tree formula image arrhythmogenic cardiomyopathy—clinically affected. formula image arrhythmogenic cardiomyopathy—asymptomatic carrier, could later manifest disease. formula image arrhythmogenic cardiomyopathy—uncertain, possibly affected. formula image arrhythmogenic cardiomyopathy—Not affected. E1 Genetic study: (− negative)/(+ positive). E2 Echocardiogram: (− negative)/(+ positive).
Figure 3
Figure 3
Ambulatory electrocardiogram of index patient IV.17.: Sinus rhythm, narrow QRS and negative T waves in V1 and flattened in V2–V3.
Figure 4
Figure 4
Cardiac CMR of index patient IV.17. The detailed study of the RV shows a non-dilated cavity, with no apparent abnormalities of the parietal contour and no evidence of fatty infiltration. The global dynamics of the right ventricle are preserved, with no alterations in segmental motility. There is no late enhancement in myocardial suppression sequences suggesting necrosis/fibrosis. (A) short axis; (B) four chambers; (C) right ventricle.
Figure 5
Figure 5
Electrocardiogram patient IV.16. Sinus rhythm, narrow Qrs, with negative T waves V1–V2 and flattened V3.
Figure 6
Figure 6
CMR patient IV.16. Right ventricle of normal volumes: end-diastole volume 70 mL/m2, end-systole volume 33 mL/m2 and normal systolic function, ejection fraction 53%. No dyskinetic areas or focal aneurysmal dilatations were observed. There is no late enhancement in myocardial suppression sequences suggesting necrosis/fibrosis. (A) short axis; (B) four chambers; (C) long axis, four chambers.
Figure 7
Figure 7
Electrocardiogram patient III.13. Sinus base rhythm T negative V1–V2 and flattened V3.
Figure 8
Figure 8
CMR patient III.13 Right ventricle with normal volumes: end-diastole volume 44 mL/m2 and end-systole volume 21 mL/m2 with preserved global systolic function, ejection fraction 52%. No late gadolinium enhancement. Four chambers; (A) Short axis; (B) Four chambers (C) Long axis.
See this image and copyright information in PMC

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