Brauch et al. (2009) studied 2 large multigenerational European American families with dilated cardiomyopathy (CMD). In 'kindred DC-12,' the patriarch, who was of Scottish ancestry, died suddenly at 39 years of age. Ten family members developed documented CMD, ... Brauch et al. (2009) studied 2 large multigenerational European American families with dilated cardiomyopathy (CMD). In 'kindred DC-12,' the patriarch, who was of Scottish ancestry, died suddenly at 39 years of age. Ten family members developed documented CMD, 2 as young children; the mean age at diagnosis was 30 years. Two underwent cardiac transplantation as young adults, and all but 3 had died of their disease (mean age at death, 37.7 years). In 'kindred DC-35,' which was of Norwegian ancestry, the proband's father died suddenly at 29 years of age. Twelve relatives had documented CMD, with a mean age at diagnosis of 41.3 years, and 5 others had suspected CMD based on sudden death and/or history alone (mean age at death, 45.7 years). Five living relatives with CMD received an implantable cardioverter-defibrillator (ICD).
Brauch et al. (2009) stated that mutations in RBM20 were associated with clinically aggressive CMD: the 39 mutation-positive patients in the 8 families were diagnosed 9 years earlier than a comparable series of patients with sporadic and familial ... Brauch et al. (2009) stated that mutations in RBM20 were associated with clinically aggressive CMD: the 39 mutation-positive patients in the 8 families were diagnosed 9 years earlier than a comparable series of patients with sporadic and familial CMD (mean age at diagnosis, 35.9 vs 45.2 years); death occurred in 11 patients at a mean age of 45.2 years, 4 underwent cardiac transplantation, and 8 received an ICD. The malignant nature of RBM20-associated CMD was further illustrated in the 32 family members with CMD by history, of whom 13 died suddenly at a mean age of 32.7 years, 3 underwent cardiac transplantation, and 3 received an ICD. There were no consistent electrocardiographic features associated with RBM20 mutation, although 9 mutation-positive patients had ventricular tachycardia.
In 2 large multigenerational families with dilated cardiomyopathy (CMD) mapping to chromosome 10q25-q26, Brauch et al. (2009) analyzed candidate genes and identified 2 different heterozygous missense mutations in exon 9 of the RMB20 gene (613171.0001 and 613171.0002, respectively) ... In 2 large multigenerational families with dilated cardiomyopathy (CMD) mapping to chromosome 10q25-q26, Brauch et al. (2009) analyzed candidate genes and identified 2 different heterozygous missense mutations in exon 9 of the RMB20 gene (613171.0001 and 613171.0002, respectively) that cosegregated with disease and were not found in 480 ethnically matched controls. DHPLC analysis of the RBM20 gene in a cohort of 278 CMD patients revealed 6 additional families with heterozygous mutations in the RBM20 gene (613171.0003-613171.0005); the mutations all clustered within exon 9 of the RBM20 gene, cosegregated with disease, and were absent in controls. There were 5 female family members who inherited a mutation but did not fulfill diagnostic criteria, 4 of whom had left ventricular enlargement but a normal ejection fraction and 1 with a normal echocardiogram.