AIMS: With more than 40 dilated cardiomyopathy (DCM)-related genes known, 
genetic analysis of patients with idiopathic DCM is costly and time-consuming. 
We describe the yield from genetic analysis in DCM patients in a large Dutch 
cohort.
METHODS AND RESULTS: We collected cardiological and neurological evaluations, 
family screenings, and genetic analyses for 418 index patients with idiopathic 
DCM. We identified 35 (putative) pathogenic mutations in 82 index patients 
(20%). The type of DCM influenced the yield, with mutations found in 25% of 
familial DCM cases, compared with 8% of sporadic DCM cases and 62% of cases 
where DCM was accompanied by neuromuscular disease. A PLN founder mutation (43 
cases) and LMNA mutations (19 cases, 16 different mutations) were most prevalent 
and often demonstrated a specific phenotype. Other mutations were found in: 
MYH7, DES, TNNT2, DMD, TPM1, DMPK, SCN5A, SGCB (homozygous), and TNNI3. After a 
median follow-up of 40 months, the combined outcome of death from any cause, 
heart transplantation, or malignant ventricular arrhythmias in patients with a 
mutation was worse than in those without an identified mutation (hazard ratio 
2.0, 95% confidence interval 1.4-3.0). This seems to be mainly attributable to a 
high prevalence of malignant ventricular arrhythmias and end-stage heart failure 
in LMNA and PLN mutation carriers.
CONCLUSION: The yield of identified mutations in DCM index patients with 
clinical clues, such as associated neuromuscular disease or familial occurrence, 
is higher compared with those without these clues. For sporadic DCM, specific 
clinical characteristics may be used to select cases for DNA analysis.