AIMS: Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS: Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). CONCLUSION: This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.
AIMS: Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS: Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). CONCLUSION: This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.
Authors: Mireia Alcalde; Oscar Campuzano; Georgia Sarquella-Brugada; Elena Arbelo; Catarina Allegue; Sara Partemi; Anna Iglesias; Antonio Oliva; Josep Brugada; Ramon Brugada Journal: Clin Res Cardiol Date: 2014-11-15 Impact factor: 5.460
Authors: Jamie D Kapplinger; Andrew P Landstrom; Benjamin A Salisbury; Thomas E Callis; Guido D Pollevick; David J Tester; Moniek G P J Cox; Zahir Bhuiyan; Hennie Bikker; Ans C P Wiesfeld; Richard N W Hauer; J Peter van Tintelen; Jan D H Jongbloed; Hugh Calkins; Daniel P Judge; Arthur A M Wilde; Michael J Ackerman Journal: J Am Coll Cardiol Date: 2011-06-07 Impact factor: 24.094
Authors: Francesca Brun; Carl V Barnes; Gianfranco Sinagra; Dobromir Slavov; Giulia Barbati; Xiao Zhu; Sharon L Graw; Anita Spezzacatene; Bruno Pinamonti; Marco Merlo; Ernesto E Salcedo; William H Sauer; Matthew R G Taylor; Luisa Mestroni Journal: J Med Genet Date: 2014-08-25 Impact factor: 6.318
Authors: Wouter P Te Rijdt; Jan Dh Jongbloed; Rudolf A de Boer; Gaetano Thiene; Cristina Basso; Maarten P van den Berg; J Peter van Tintelen Journal: Eur J Hum Genet Date: 2013-06-05 Impact factor: 4.246