Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation. Methods: Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease. Results: The percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p<0.001), mostly due to variants of unknown significance (VUS) in TTN. The detection rate of rare variants in TTN was not significantly different to that found in the group of patients without structural heart disease. In the NGS cohort, 4 patients (1.3%) had pathogenic CNVs: 2 deletions in MYBPC3 and 2 deletions involving the complete coding region of PLN. Conclusions: A small percentage of HCM cases without point mutations in the 5 main genes are explained by P/LP variants in minor or candidate genes and CNVs. Screening for variants in TTN in HCM patients drastically increases the number of inconclusive tests, and shows a rate of VUS that is similar to patients without structural heart disease, suggesting that this gene should not be analyzed for clinical purposes in HCM

On the effect of electric field application during the curing process on the electrical conductivity of single-walled carbon nanotubes–epoxy composites

Single-walled carbon nanotube (SWCNT)/epoxy composites were cured under external electric fields andthe influence of the processing parameters (electric field magnitude and frequency, SWCNT concentrationand curing temperature) on the electrical response of the system was evaluated. A mold for theelectric field application was designed and manufactured, allowing in situ measurements of the electricalresistivity of the composite, during and after the curing process. The resulting electrical propertiesrevealed a strong dependence on the processing parameters. By rising the curing temperature, the solidbulk resistivity was decreased by one order of magnitude. Further reduction was observed with electricfields, up to an additional order of magnitude. Such improvements can be related with the decrease inviscosity and improvement of interconnected-nanotube paths within the polymer matrix. The effect ofthe electric field on the rotation and interconnection of the SWCNTs was investigated using a classicalmechanics model based on the dielectrophoretic theory for the liquid state. The influence of internanotubedistances on the bulk electrical properties was calculated at different particle concentrations,using finite element models of the microstructure. This processing technique presents promisingresults for enhancing the electrical conductivity of polymer composites with carbon-based nanoparticle