NCCM with DCM (53%) was associated with LV systolic dysfunction (p < 0.001), increased risk for major adverse cardiac events, mutations in the tail of MYH7 (p < 0.001), and DCM without NCCM in relatives (p < 0.001).
Likely pathogenic variants were found in three ARVC cases (12%) in PKP2, DSC2 or DSP, two DCM cases (20%) in MYH7, and four HCM cases (27%) in MYBPC3 (3) or MYH7 (1).
As a result, 7 novel mutations (MYPN, p.E630K; TNNT2, p.G180A; MYH6, p.R1047C; TNNC1, p.D3V; DES, p.R386H; MYBPC3, p.C1124F; and MYL3, p.D126G), 3 variants of uncertain significance (RBM20, p.R1182H; MYH6, p.T1253M; and VCL, p.M209L), and 2 known mutations (MYH7, p.A26V and MYBPC3, p.R160W) were revealed to be associated with DCM.
The presumed pathogenic mutations were distributed with one case of suspected HCM and DCM (MYH7; p.R442H), one case of suspected DCM (LMNA; p.R471H), and two cases of suspected ARVC (PKP2; p.R79X and LMNA; p.R644C).
Interestingly, this correlation and a link between MYH7 mutations and a higher degree of mitral valve regurgitation held true for both HCM and DCM, indicating that the gene affected by a mutation may determine the magnitude of structural and functional alterations in both HCM and DCM.
Multivariate analyses to examine the joint effects of multiple gene variants confirmed univariate results for MYH7 and TCAP and identified a block of nine variants in MYH7 that was strongly associated with DCM.
About 130 consecutive patients diagnosed with HCM or DCM (69 with HCM and 61 with DCM) attending the cardiology clinic of Post Graduate Institute of Medical Education and Research were screened for mutations in the MYH7 gene.
Conclusion These results confirm the genetic heterogeneity of NCCM and suggest that the molecular classification of cardiomyopathies includes an MYH7-associated spectrum of NCCM with HCM, RCM, and DCM.