Cardiomyopathy, Dilated, 1cc

A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1CC (CMD1CC) is caused by heterozygous mutation in the nexilin gene (NEXN; 613121) on chromosome 1p31.

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

Hassel et al. (2009) reported 9 patients with CMD due to an NEXN mutation with onset of dilated cardiomyopathy in the fifth or sixth decade of life. The average left ventricular end-diastolic diameter was approximately 69 mm, and average left ventricular ejection fraction was approximately 26%. One patient underwent heart transplantation at age 60 years due to progressive dilated cardiomyopathy.

Because of evidence that loss of nexilin leads to severe cardiomyopathy in zebrafish, Hassel et al. (2009) analyzed the NEXN gene in 90 patients diagnosed with idiopathic dilated cardiomyopathy (CMD) and identified heterozygosity for a 3-bp deletion affecting a conserved gly650 residue in 2 patients (G650del; 613121.0001). Screening of the entire NEXN coding sequence in an additional 910 CMD patients revealed the G650del mutation in 4 more patients; in addition, 2 heterozygous missense mutations were detected, Y652C in 2 patients (613121.0002) and P611T in 1 patient (613121.0003). All mutation-positive patients were screened for mutations in other known CMD-associated genes, but no mutations were identified, and none of the NEXN mutations were found in 1,251 age-, gender-, ethnicity- and geography-matched controls. Screening of family members of the affected mutation carriers identified 4 additional carriers of the G650del mutation, including 2 individuals who had died from dilated cardiomyopathy, 1 with borderline clinical findings, and a 33-year-old asymptomatic female who declined further evaluation. Haplotype analysis suggested distinct founder effects for both the G650del and Y652C mutations.