PKP2 and DSG2 genetic variations in Latvian arrhythmogenic right ventricular dysplasia/cardiomyopathy registry patientsLuize Bidina1, Kaspars Kupics2, Emma Sokolova3, Mihails Pavlovics4, Zane Dobele1, Laima Caunite3, Oskars Kalejs2, Linda Gailite1
1Scientific Laboratory of Molecular Genetics; Riga-Latvia
2Department of Arrhytmology, Pauls Stradins Clinical University Hospital; Riga-Latvia
3Department Cardiology, Pauls Stradins Clinical University Hospital; Riga-Latvia
4Department of Surgery, Pauls Stradins Clinical University Hospital; Riga-Latvia
Objective: The Latvian arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD-C) registry was established to determine the genetic background of ARVD-C for analyzing discovered genetic variation frequencies in the European and Latvian populations.Keywords: arrhythmogenic right ventricular dysplasia-cardiomyopathy, ARVD-C, cardiomyopathy, genetics, PKP2, arrhythmia
Methods: In total, 38 patients with suspected ARVD-C were selected. The clinical parameters were defined according to the ARVD-C guidelines, PKP2 and DSG2 gene analysis was performed using the Sanger sequencing. Additionally, large deletions/duplications were analyzed using the multiplex ligation-dependent probe amplification (MLPA) analysis.
Results: Twenty symptomatic patients were enrolled in the study. Typical ARVD abnormalities were found in electrocardiography for 10 (50%) patients, in Holter monitoring for 19 (95%), in transthoracic echocardiography for 20 (100%), and in cardiac magnetic resonance for 6 (30%). Different benign genetic variations were found. Three novel, unregistered, possibly benign variations were found in the PKP2 gene: c.2489+131G>A, c.2489+72delA, and c.1035-5T>C and three in the DSG2 gene: c.404G>A, c.1107G>A, and c.379-15A>G. Two genetic variations in the PKP2 gene: c.1592T>G, c.2489+1G>A are possibly pathogenic. For the first time, variation c.1592T>G, has been discovered in the homozygote form. Using the MLPA analysis, large deletions or duplications were not found.
Conclusion: The prevalence of the majority of non-pathological genetic variations is similar in the Latvian ARVD-C patients and the European population. Possibly, pathogenic variations were found only in 10% of our registry patients, which could mean that PKP2 and DSG2 are not the most commonly affected genes in the Latvian population.
Luize Bidina, Kaspars Kupics, Emma Sokolova, Mihails Pavlovics, Zane Dobele, Laima Caunite, Oskars Kalejs, Linda Gailite. PKP2 and DSG2 genetic variations in Latvian arrhythmogenic right ventricular dysplasia/cardiomyopathy registry patients. Anatol J Cardiol. 2018; 20(5): 296-302
Sorumlu Yazar: Luize Bidina, Latvia