Cardiomyopathy, Dilated, 1o
A number sign (#) is used with this entry because this form of cardiomyopathy can be caused by mutation in the ABCC9 gene (601439).
For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200).
Bienengraeber et al. (2004) performed mutation scans of K(ATP) (ATP-sensitive potassium) channel genes in 323 individuals, predominantly of European descent, with idiopathic dilated cardiomyopathy. They identified 2 heterozygous mutations in the ABCC9 gene, both in exon 38, which encodes the C-terminal domain of SUR2A specific to the cardiac splice variant of the regulatory K(ATP) channel subunit. Both individuals with mutations in ABCC9 had severely dilated hearts with compromised contractile function and rhythm disturbances. The first patient, a male with no family history of dilated cardiomyopathy, was diagnosed at age 55 and died from heart failure at age 60. The second patient was a female diagnosed at age 40. Her father was diagnosed at age 54 and died at age 55 from heart failure. All affected individuals had ventricular tachycardia and normal coronary angiography. The mutations identified resulted in dysfunction of the SUR2A subunit by disruption of the C terminus. Bienengraeber et al. (2004) suggested that these defects in the regulatory K(ATP) channel subunit disrupt catalysis-dependent gating and impair metabolic decoding, establishing a theretofore unrecognized mechanism of channel malfunction in human disease.