BACKGROUND: Muscle LIM protein (MLP) is an essential nuclear regulator of 
myogenic differentiation. Additionally, it may act as an integrator of protein 
assembly of the actin-based cytoskeleton. MLP-knockout mice develop a marked 
cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore 
a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and 
DCM in humans.
METHODS AND RESULTS: We analyzed 1100 unrelated individuals (400 patients with 
DCM, 200 patients with HCM, and 500 controls) for mutations in the human CRP3 
gene that encodes MLP. We found 3 different missense mutations in 3 unrelated 
patients with familial HCM but detected no mutation in the DCM group or the 
controls. All mutations predicted an amino acid exchange at highly conserved 
residues in the functionally important LIM1 domain, which is responsible for 
interaction with alpha-actinin and with certain muscle-specific transcription 
factors. Protein-binding studies indicate that mutations in the CRP3 gene lead 
to a decreased binding activity of MLP to alpha-actinin. All 3 index patients 
were characterized by typical asymmetrical septal hypertrophy. Family studies 
revealed cosegregation of clinically affected individuals with the respective 
mutations in MLP.
CONCLUSION: Here, we present evidence that mutations in the CRP3/MLP gene can 
cause HCM.