title: Arrhythmogenic Right Ventricular Cardiomyopathy - 4 Swedish families with an associated PKP2 c.2146-1G>C variant.
abstract: In this study, the genotype-phenotype correlations in four unrelated families with a PKP2 c.2146-1G>C gene variant were studied. Our primary aim was to determine the carriers that fulfilled the arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnostic criteria of 2010. Our secondary aim was to investigate whether any specific clinical characteristics can be attributed to this particular gene variant. Index patients were assessed using next generation ARVC panel sequencing technique and their family members were assessed by Sanger sequencing targeted at the PKP2 c.2146-1G>C variant. The gene variant carriers were offered a clinical follow-up, with evaluation based on the patient's history and a standard set of non-invasive testing. The PKP2 c.2146-1G>C gene variant was found in 23 of 41 patients who underwent the examination. Twelve of the 19 family members showed "possible ARVC". One with "borderline ARVC" and the rest with "definite ARVC" demonstrated re-polarization disturbances, but arrhythmia was uncommon. A lethal event occurred in a 14-year-old boy. In the present study, no definitive genotype-phenotype correlations were found, where the majority of the family members carrying the PKP2 c.2146-1G>C gene variant were diagnosed with "possible ARVC". These individuals should be offered a long-term follow-up since they are frequently symptomless but still at risk for insidious sudden cardiac death due to ventricular arrhythmia.
authors.affiliation: Department of Cardiology and Department of Medical and Health Sciences, Linköping University Linköping, Sweden.
authors.forename: Anneli
authors.initials: A
authors.lastname: Svensson
authors.affiliation: Department of Clinical Physiology and Department of Medical and Health Sciences, Linköping University Linköping, Sweden.
authors.forename: Meriam
authors.initials: M
authors.lastname: Åström-Aneq
authors.affiliation: Department of Clinical Pathology and Clinical Genetics, and Department of Clinical Experimental Medicine, Linköping University Linköping, Sweden.
authors.forename: Kjerstin Ferm
authors.initials: KF
authors.lastname: Widlund
authors.affiliation: Department of Cardiology and Department of Medical and Health Sciences, Linköping University Linköping, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Fluur
authors.affiliation: Department of Clinical Pathology and Clinical Genetics, and Department of Clinical Experimental Medicine, Linköping University Linköping, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Green
authors.affiliation: Department of Clinical Pathology and Clinical Genetics, and Department of Clinical Experimental Medicine, Linköping University Linköping, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Rehnberg
authors.affiliation: Department of Clinical Pathology and Clinical Genetics, and Department of Clinical Experimental Medicine, Linköping University Linköping, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gunnarsson
keywords: ARVC; PKP2; heredity; sudden cardiac death