Novel mutations in β-MYH7 gene in Indian patients with dilated cardiomyopathy

Abstract Background Heart failure is a hallmark of severe hypertrophic (HCM) and dilated (DCM) cardiomyopathies. Several mutations in the β-MYH7 gene lead to HCM. Recently, causative mutations in the β-MYH7 gene have also been detected in DCM from different populations. Methods Here, we sequenced the β-MYH7 gene in 137 Indian DCM patients and 167 ethnically matched healthy controls to detect the frequency of mutations and their association. Results Our study revealed 27 variations, of which seven mutations (8.0%) were detected exclusively in Indian DCM patients for the first time. These included four missense mutations: Arg723His, Phe510Leu, His358Leu, and Ser384Tyr (2.9%), a frameshift mutation: Asn676_T-del (1.5%), and two splice-site mutations (IVS17+2T) T>G & (IVS19-1G) G>A (3.6%). Remarkably, all four missense mutations altered evolutionarily conserved amino acids. All four missense mutations were predicted pathogenic by Polymorphism phenotyping v2 (Polyphen-2) and Sorting Intolerant From Tolerant (SIFT), two bioinformatics tools. In addition, the four p.Leu358, p.Tyr384, p.Leu510, and p.His723 homology models of β-MYH7 displayed root-mean-square deviation (RMSD) of ∼2.55A0, ∼1.24A0, ∼3.36A0, and ∼3.86A0, respectively. Conclusion In the present study, we detected numerous novel, unique, and rare mutations in the β-MYH7 gene exclusively in Indian DCM patients (8.0%). Here, we demonstrated how each mutant (missense) uniquely disrupts a critical network of non-bonding interactions at the mutation site (molecular level) and may contribute to dilated cardiomyopathy (DCM). Therefore, our findings may provide insight into understanding the molecular bases of disease, diagnosis and promote novel therapeutic strategies (personalized medicine).