Biochemical and Biophysical Research Communications
Novel mutations in sarcomeric protein genes in dilated cardiomyopathy
Section snippets
Materials and methods
Clinical evaluation. This study is based on 46 unrelated patients with a diagnosis of DCM, who gave written informed consent for genotyping and detailed prospective phenotyping. The study was approved by the Ethic Committee of Charité, Humboldt University Berlin. Thirty eight of 46 patients were male, eight female. The patients’ age at study was 35±8 years; the age at diagnosis was 29±8 years. Diagnosis was based on echocardiography, coronary angiography, and in selected cases, endomyocardiac
Results
By systematic mutation screening of 46 DCM patients using SSCP analysis we identified a total of three mutations, two in MYH7 and one in MYBPC3. All three mutations lead to the substitution of an amino acid. In addition, we found a number of silent variants and polymorphisms, which were partially already detected in HCM (Table 1, Table 2).
In exon 8 of MYH7 a G to A transition occurs in one male patient at nucleotide 7799 (GenBank No. M57965). This mutation is predicted to result in the
Discussion
The novel findings of our study consist in the detection of three novel rare mutations, leading to amino acid exchanges in the HCM related genes MYH7 and MYBPC3 in patients with DCM.
Inspection of the protein structure of β-MHC predicts effects on thermostability and protein folding for the mutation Ala223Thr and severe conformational changes for Ser642Leu located close to the actin–myosin interaction site. Both mutations did not occur in healthy controls or HCM patients. Since both occurred in
Acknowledgements
The study was Supported by BMBF, Grant NBL III, TP3.1.4.
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