Cardiomyopathy, Dilated, 1bb
A number sign (#) is used with this entry because of evidence that susceptibility to dilated cardiomyopathy is associated with variation in the desmoglein-2 gene (DSG2; 125671).
For a phenotypic description and discussion of genetic heterogeneity in dilated cardiomyopathy, see CMD1A (115200).
Molecular GeneticsIn a man with dilated cardiomyopathy who had severely decreased cardiac function and underwent cardiac transplantation at 44 years of age, Posch et al. (2008) identified homozygosity for the V55M mutation in the DSG2 gene (125671.0009). The proband's father, who had less severe disease with a later onset, was heterozygous for the mutation, as was his asymptomatic mother; his paternal grandfather had died of heart failure at 57 years of age. The proband had no abnormalities of skin or hair. Posch et al. (2008) subsequently screened 538 CMD patients for the DSG2 V55M variant and identified 13 unrelated carriers (2.4%); the variant was also found in 1 (0.23%) of 432 individuals without CMD (p less than 0.006). In a total of 1,228 cases and controls, the authors found significant association between the DSG2 V55M variant and CMD (p less than 0.007). Immunostaining and electron microscopy of explanted left ventricular wall myocardium from the homozygous proband revealed pale, irregularly shaped intercalated discs with an indistinct inner structure and significantly shorter desmosomes compared to wildtype.