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An estimated 77 probands with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are screened for mutations in desmocollin-2 (DSC2), a gene coding for a desmosomal cadherin. The heterozygous mutations, which are identified in four probands, result in frameshifts and premature truncation of the desmocollin-2 protein, which is consistent with the hypothesis that ARVD/C is a disease of the desmosome.

Primary congenital lymphedema (PCL), or Milroy disease or hereditary lymphedema type I, has been mapped to the 5q35.3 region. A genomewide search has been done using a 4-generation Irish-descent family in North America with dominantly inherited PCL. Four additional British families were studied and linkage to markers from the 5q35.3 region in the five families was achieved. Four unaffected subjects were carriers; the estimated penetrance ratio for PCL is .84. Several mapped genes in the 5q35 region are potentially involved in PCL etiology.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited myocardial disorder associated with arrhythmias, heart failure, and sudden death. To date, mutations in four genes encoding major desmosomal proteins (plakoglobin, desmoplakin, plakophilin-2, and desmoglein-2) have been implicated in the pathogenesis of ARVD/C. We screened 77 probands with ARVD/C for mutations in desmocollin-2 (DSC2), a gene coding for a desmosomal cadherin. Two heterozygous mutations—a deletion and an insertion—were identified in four probands. Both mutations result in frameshifts and premature truncation of the desmocollin-2 protein. For the first time, we have identified mutations in desmocollin-2 in patients with ARVD/C, a finding that is consistent with the hypothesis that ARVD/C is a disease of the desmosome. [ABSTRACT FROM AUTHOR]