Response to: Milting H and Klauke B (2008) Molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Nat Clin Prac Cardioasc Med doi:10.1038/ncpcardio1350

Original article: Awad MM et al. (2008) Mechanisms of Disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Nat Clin Prac Cardiovasc Med 5: 258–267 doi:10.1038/ncpcardio1182

I thank Drs Milting and Klauke for reporting further characterization of this DSG2 allele. As they noted, our study group included a desmoglein-2 mutation, E712K which corresponds to the more widely accepted sequence annotation as E713K.1 Although we were not able to reference the primary report of every sequence alteration in Figure 2, Biedermann and colleagues previously reported that E712K is over-represented among individuals with familial gastric cancer compared to those with sporadic gastric cancer, suggesting a pathogenic role for this variant.2 In our Review, we attempted to include all published sequence variants with purported pathogenic effects and we did not include our own unpublished data.

Since then, we have assessed the prevalence of this allele in our own ARVD/C cohort as well as 200 North American Caucasian controls from Coriell Institute. We agree with Drs Milting and Klauke that this variant is a common SNP among Caucasians and is not likely pathogenic among individuals with ARVD/C.

Table 1
Full size table