Cardiomyopathy, Dilated, 1v

A number sign (#) is used with this entry because dilated cardiomyopathy-1V is caused by heterozygous mutation in the PSEN2 gene (600759) on chromosome 1q31-q42.

For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200).

Li et al. (2006) described 2 families with dilated cardiomyopathy segregating with mutation in the PSEN2 gene (CMD1V). The mutation was present in heterozygous state. Both were white families. Onset of cardiovascular disease occurred at the age of 48 to 55 years in one family. A mutation-positive family member had normal results on cardiovascular screening, suggesting reduced penetrance. One obligate carrier from the same family had the onset of dementia at age 75 years without evidence of cardiovascular disease. In the second family, 3 sibs received the diagnosis of DCM between ages 36 and 45 years. Two of the 5 mutation carriers in this family aged more than 35 years did not show evidence of cardiovascular disease, suggesting reduced penetrance and/or variable age at onset.

Li et al. (2006) hypothesized that, since the presenilins are expressed in the heart and are critical to cardiac development, mutations in presenilins may also be associated with dilated cardiomyopathy. They evaluated a total of 315 index patients with DCM for sequence variation in PSEN1 (104311) and PSEN2. In 2 families, Li et al. (2006) found that idiopathic dilated cardiomyopathy segregated with a ser130-to-leu amino acid change (S130L; 600759.0008). This mutation had been reported in association with Alzheimer disease (606889) in a small kindred by Tedde et al. (2003). Li et al. (2006) also identified a novel mutation in the PSEN1 gene (104311.0034) in one family (CMD1U; 613694). Families positive for mutations underwent additional clinical, genetic, and functional studies. The PSEN1 mutation was associated with complete penetrance and progressive disease that resulted in the necessity of cardiac transplantation or in death. The PSEN2 mutation showed partial penetrance, milder disease, and a more favorable prognosis. Calcium signaling was altered in cultured fibroblasts from PSEN1 and PSEN2 mutation carriers.