Cardiomyopathy, Dilated, 1nn
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1NN (CMD1NN) is caused by heterozygous mutation in the RAF1 gene (164760) on chromosome 3p25.
For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200).
Clinical FeaturesDhandapany et al. (2014) reported patients with nonsyndromic dilated cardiomyopathy (CMD) and mutations in the RAF1 gene (see MOLECULAR GENETICS). Of 10 patients in whom age of onset was known, 8 presented in childhood or adolescence. The average age at presentation was 12.6 years, which the authors noted was younger than the approximate average of 20 years associated with CMD caused by sarcomeric gene mutations.
Molecular GeneticsIn 218 patients from South India with nonsyndromic dilated cardiomyopathy, Dhandapany et al. (2014) analyzed 9 RAS-MAPK genes and identified 4 heterozygous mutations in the RAF1 gene (see, e.g., 164760.0005 and 164760.0006) in 5 of the CMD probands. The RAF1 mutations were not found in 500 ancestry-matched controls or in 13,600 European and African American alleles in the Exome Sequencing Project database; in addition, the 5 probands were negative for mutation in 12 known cardiomyopathy genes. Dhandapany et al. (2014) screened 200 North Indian, 35 Japanese, and 60 Italian probands with CMD for mutations in RAF1 and identified 2 different heterozygous mutations in 2 North Indian patients (see, e.g., 164760.0006) and 2 in 2 Japanese patients (see, e.g., 164760.0007).