In this study we defined the pathogenic effects of three DCM-causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3<sub>p.98truncation</sub> ) and cardiac troponin T (TNNT2<sub>p.K217deletion</sub> ; also known as the p.K210del) and the non-sarcomeric gene mutation encoding lamin A/C (LMNA<sub>p.R331Q</sub> ).
V54M mutation found in the hydrophobic core region of the protein associated with abnormal clinical phenotype leads to DCM was selected for further analysis.
To explore the novel disease gene for DCM, we examined CRYAB encoding alphaB-crystallin for mutation in the patients with DCM, since alphaB-crystallin was recently reported to associate with the heart-specific N2B domain and adjacent I26/I27 domain of titin/connectin, and we previously reported a N2B mutation, Gln4053ter, in DCM.
In another large family with DCM linked to CMD1G, a TTN missense mutation (Trp930Arg) is predicted to disrupt a highly conserved hydrophobic core sequence of an immunoglobulin fold located in the Z-disc-I-band transition zone.