BACKGROUND: We report an Italian family in which the proband showed a severe 
phenotype characterized by the association of congenital fiber type 
disproportion (CFTD) with a left ventricular non-compaction cardiomyopathy 
(LVNC). This study was focused on the identification of the responsible gene/s.
METHODS AND RESULTS: Using the whole-exome sequencing approach, we identified 
the proband homozygous missense mutations in two genes, the myosin heavy chain 
7B (MYH7B) and the integrin alpha 7 (ITGA7). Both genes are expressed in heart 
and muscle tissues, and both mutations were predicted to be deleterious and were 
not found in the healthy population.The R890C mutation in the MYH7B gene 
segregated with the LVNC phenotype in the examined family. It was also found in 
one unrelated patient affected by LVNC, confirming a causative role in 
cardiomyopathy.The E882K mutation in the ITGA7 gene, a key component of the 
basal lamina of muscle fibers, was found only in the proband, suggesting a role 
in CFTD.
CONCLUSIONS: This study identifies two novel disease genes. Mutation in MYH7B 
causes a classical LVNC phenotype, whereas mutation in ITGA7 causes CFTD. Both 
phenotypes represent alterations of skeletal and cardiac muscle maturation and 
are usually not severe. The severe phenotype of the proband is most likely due 
to a synergic effect of these two mutations.This study provides new insights 
into the genetics underlying Mendelian traits and demonstrates a role for 
digenic inheritance in complex phenotypes.