Novel Mutations in β-MYH7 Gene in Indian Patients With Dilated Cardiomyopathy
Deepa Selvi Rani, Archana Vijaya Kumar, Pratibha Nallari, Katakam Sampathkumar, Perundurai S. Dhandapany, Calambur Narasimhan, Andiappan Rathinavel, Kumarasamy Thangaraj
Abstract
BACKGROUND: gene have also been detected in DCM from different populations. METHODS: 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 7 mutations (8.0%) were detected exclusively in Indian DCM patients for the first time. These included 4 missense mutations-Arg723His, Phe510Leu, His358Leu, and Ser384Tyr (2.9%); a frameshift mutation-Asn676_T-del (1.5%); and 2 splice-site mutations (IVS17+2T) T>G and (IVS19-1G) G>A (3.6%). Remarkably, all 4 missense mutations altered evolutionarily conserved amino acids. All 4 missense mutations were predicted to be pathogenic by 2 bioinformatics tools-polymorphism phenotyping v2 (PolyPhen-2) and sorting intolerant from tolerant (SIFT). In addition, the 4 homology models of β-MYH7-p.Leu358, p.Tyr384, p.Leu510, and p.His723-displayed root-mean-square deviations of ∼2.55 Å, ∼1.24 Å, ∼3.36 Å, and ∼3.86 Å, respectively. CONCLUSIONS: 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 development of dilated cardiomyopathy (DCM). Therefore, our findings may provide insight into the understanding of the molecular bases of disease and into diagnosis along with promoting novel therapeutic strategies (through personalized medicine).