AIMS: Familial dilated cardiomyopathy (FDCM) is associated with mutations in 
more than 10 genes, but genes mutation frequencies and associated clinical 
features remain largely unknown. Here, we performed a mutation analysis of four 
genes involved in FDCM in a population of idiopathic DCM.
METHODS AND RESULTS: A SSCP and sequencing mutation screening of all the exons 
coding for beta myosin heavy chain (MYH7 gene), cardiac T troponin (TNNT2 gene), 
phospholamban (PLN gene), and the cardio-specific exon of metavinculin (VCL 
gene) were performed in 96 independent patients (54 familial and 42 sporadic). 
It led to the identification of eight heterozygous mutations, seven new ones in 
MYH7, and the already described R141W mutation in TNNT2. MYH7 mutations (in five 
familial and two sporadic cases) substitute residues located either in the head 
(I201T, T412N, A550V) or tail domains (T1019N, R1193S, E1426K, R1634S) of the 
protein. DCM was not associated with skeletal myopathy or conduction defects in 
any patients. Contrasting clinical features were observed between MYH7 and TNNT2 
mutations carriers. In MYH7 vs. TNNT2, mean age at diagnosis was late (P<0.03), 
penetrance was incomplete in adults (56 vs. 100%), and mean age at major cardiac 
event was higher (P<0.04).
CONCLUSION: We have identified seven mutations in MYH7, one in TNNT2, and none 
in PLN or in the VCL cardio-specific exon. MYH7 appears as the most frequently 
mutated gene in our FDCM population (approximately 10%), and mutation carriers 
present with delayed onset, in contrast to TNNT2.