Article

Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia

Institut de Cardiologie de Montréal, Montréal, Québec, Canada.
Clinical Genetics (Impact Factor: 3.65). 10/2009; 77(1):37-48. DOI: 10.1111/j.1399-0004.2009.01282.x
Source: PubMed

ABSTRACT In a cohort of patients with confirmed or suspected arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), genetic testing is useful in confirming the diagnosis, particularly in individuals who do not completely fulfil Task Force criteria for the disease, thereby also enabling the adoption of preventive measures in family members. Due to the high percentage of novel mutations that are expected to be identified in ARVC/D, the use of genetic screening technology based on the identification of known mutations seems to have very restricted value. Our results support that the presence of certain genetic variations could play a role in the final phenotype of patients with ARVC/D, where single and compound mutation carriers would have more symptomatic forms of the disease and the polymorphism P366L could be associated to a more benign phenotype.

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    • "The EC1 domain of DSC2 exhibits potentially destabilising ARVC-linked mutations including G150A, R203C, R203H, G220R, and I231T [64] [68] [69] [89]. ARVC-linked pathogenic mutations in the EC2 domain of DSC2 include T275M, P292S, T340A, I342V, I345T, and D350Y, with the latter mutation removing a Ca 2+ coordinating group that rigidifies the linkage to EC3 [52] [54] [64] [89]. The E102K and I345T mutant DSC2 proteins delocalize from the plasma membrane to the cytosol [90], inferring trafficking defects, while the R203C and T275M mutants show impaired proteolytic processing [64]. "
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    • "The EC1 domain of DSC2 exhibits potentially destabilising ARVC-linked mutations including G150A, R203C, R203H, G220R, and I231T [64] [68] [69] [89]. ARVC-linked pathogenic mutations in the EC2 domain of DSC2 include T275M, P292S, T340A, I342V, I345T, and D350Y, with the latter mutation removing a Ca 2+ coordinating group that rigidifies the linkage to EC3 [52] [54] [64] [89]. The E102K and I345T mutant DSC2 proteins delocalize from the plasma membrane to the cytosol [90], inferring trafficking defects, while the R203C and T275M mutants show impaired proteolytic processing [64]. "
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