Cardiomyopathy, Dilated, 1kk

A number sign (#) is used with this entry because of evidence that cardiomyopathy of the dilated (CMD1KK), hypertrophic (CMH22), or restrictive (RCM4) type can be caused by heterozygous mutation in the myopalladin gene (MYPN; 608517) on chromosome 10q21.

For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see 115200; for hypertrophic cardiomyopathy, see 192600; for familial restrictive cardiomyopathy, see 115210.

Duboscq-Bidot et al. (2008) studied 6 patients from 2 families, as well as 2 sporadic patients, with isolated dilated cardiomyopathy due to mutations in the myopalladin gene (see MOLECULAR GENETICS). Mean age at diagnosis was 40 years. Of the 8 patients, 4 had incomplete left bundle branch block (BBB) on electrocardiogram, 1 had complete left BBB, and 1 had right BBB; 3 patients had left ventricular hypertrophy. There were 3 cardiac deaths due to refractory congestive heart failure, at 20, 29, and 55 years of age. Immunofluorescence analysis of explanted cardiac tissue from 1 of the patients demonstrated labeling of the functionally normal right ventricle that was indistinguishable from controls, whereas the dilated left ventricle showed reduced localization of myopalladin to the Z-band region.

Duboscq-Bidot et al. (2008) screened 114 probands with dilated cardiomyopathy (CMD) for mutations in the MYPN gene (608517) and identified 4 heterozygous mutations, in 2 (3%) of 65 familial cases and 2 (4%) of 49 sporadic cases, respectively (see, e.g., 608517.0001-608517.0003). The familial mutations segregated fully with disease in 1 pedigree and with variable penetrance in the other, and none of the mutations were found in 400 ethnically matched controls.

Purevjav et al. (2012) screened the MYPN gene in 900 unrelated patients with cardiomyopathy, including 484 with hypertrophic cardiomyopathy (CMH), 348 with CMD, and 68 with restrictive cardiomyopathy (RCM), and identified 15 rare sequence variants. A P1112L missense mutation (608517.0002), previously identified in a CMD patient by Duboscq-Bidot et al. (2008), was detected in a patient with CMH; another missense mutation, Y20C (608517.0004), was identified in 1 patient with CMD and another with CMH; and a nonsense mutation (Q529X; 608517.0005) was identified in 2 sibs with RCM. The overall prevalence of MYPN mutations was 1.66%, with 1.72% for CMD, 1.86% for CMH, and 1.45% for RCM; the authors noted that this relatively high prevalence compared to other reported disease genes suggests that MYPN is likely to be clinically important.

Meyer et al. (2013) analyzed the MYPN and ANKRD1 (609599) genes in 255 unrelated consecutive patients with CMD and identified 2 heterozygous missense mutations in the MYPN gene (see, e.g., 608517.0006) in 2 patients, for a prevalence of 0.8%. No disease-related mutations were found in ANKRD1.