Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia

Barbara Bauce, Andrea Nava, Giorgia Beffagna, Cristina Basso, Alessandra Lorenzon, Gessica Smaniotto, Marzia De Bortoli, Ilaria Rigato, Elisa Mazzotti, Alexandros Steriotis, Martina Perazzolo Marra, Jeffrey Towbin, Gaetano Thiene, Gian Antonio Danieli, Alessandra Rampazzo

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a progressive cardiomyopathy showing a wide clinical spectrum in terms of clinical expressions and prognoses. Objective: This study sought to estimate the occurrence of compound and double heterozygotes for mutations in desmosomal proteins encoding genes in a cohort of ARVC/D Italian index cases, and to assess the clinical phenotype of mutations carriers. Methods: Fourty-two consecutive ARVC/D index cases who fulfilled the International Task Force diagnostic criteria were screened for mutations in PKP2, DSP, DSG2, DSC2, and JUP genes by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. Results: Three probands (7.1%) showing a family history of sudden death carried multiple mutations. Family screening identified an additional 7 multiple-mutation carriers. Among the 7 double heterozygotes for mutations in different genes, 2 were clinically unaffected, 2 were affected, and 3 showed some clinical signs of ARVC/D even if they did not fulfill the diagnostic criteria. Two compound heterozygotes for mutations in the same gene and 1 subject carrying 3 different mutations showed a severe form of the disease with heart failure onset at a young age. Moreover, multiple-mutation carriers showed a higher prevalence of left ventricular involvement (P = .025) than single-mutation carriers. Conclusion: Occurrence of compound and double heterozygotes in ARVC/D index cases is particularly relevant to mutation screening strategy and to genetic counseling. Even if multiple-mutation carriers show a wide variability in clinical expression, the extent of the disease is higher compared to that in single-mutation carriers.

Original languageEnglish (US)
Pages (from-to)22-29
Number of pages8
JournalHeart Rhythm
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Arrhythmogenic Right Ventricular Dysplasia
Mutation
Proteins
Heterozygote
Genes
Genetic Counseling
Advisory Committees
Sudden Death
Cardiomyopathies

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Bauce, B., Nava, A., Beffagna, G., Basso, C., Lorenzon, A., Smaniotto, G., ... Rampazzo, A. (2010). Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm, 7(1), 22-29. https://doi.org/10.1016/j.hrthm.2009.09.070

Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. / Bauce, Barbara; Nava, Andrea; Beffagna, Giorgia; Basso, Cristina; Lorenzon, Alessandra; Smaniotto, Gessica; De Bortoli, Marzia; Rigato, Ilaria; Mazzotti, Elisa; Steriotis, Alexandros; Marra, Martina Perazzolo; Towbin, Jeffrey; Thiene, Gaetano; Danieli, Gian Antonio; Rampazzo, Alessandra.

In: Heart Rhythm, Vol. 7, No. 1, 01.01.2010, p. 22-29.

Research output: Contribution to journalArticle

Bauce, B, Nava, A, Beffagna, G, Basso, C, Lorenzon, A, Smaniotto, G, De Bortoli, M, Rigato, I, Mazzotti, E, Steriotis, A, Marra, MP, Towbin, J, Thiene, G, Danieli, GA & Rampazzo, A 2010, 'Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia', Heart Rhythm, vol. 7, no. 1, pp. 22-29. https://doi.org/10.1016/j.hrthm.2009.09.070
Bauce, Barbara ; Nava, Andrea ; Beffagna, Giorgia ; Basso, Cristina ; Lorenzon, Alessandra ; Smaniotto, Gessica ; De Bortoli, Marzia ; Rigato, Ilaria ; Mazzotti, Elisa ; Steriotis, Alexandros ; Marra, Martina Perazzolo ; Towbin, Jeffrey ; Thiene, Gaetano ; Danieli, Gian Antonio ; Rampazzo, Alessandra. / Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. In: Heart Rhythm. 2010 ; Vol. 7, No. 1. pp. 22-29.
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AU - Smaniotto, Gessica

AU - De Bortoli, Marzia

AU - Rigato, Ilaria

AU - Mazzotti, Elisa

AU - Steriotis, Alexandros

AU - Marra, Martina Perazzolo

AU - Towbin, Jeffrey

AU - Thiene, Gaetano

AU - Danieli, Gian Antonio

AU - Rampazzo, Alessandra

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