Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.

The clinical spectrum of ATTRwt is heterogeneous and differs from the classic phenotype: women are affected in a significant proportion; asymmetric LV hypertrophy and impaired LVEF are not rare and only a minority have low QRS voltages. Clinicians should be aware of the broad clinical spectrum of ATTRwt to correctly identify an entity for which a number of disease-modifying treatments are under investigation.

Frequency analysis of the rf emission of oscillating Josephson supercurrent is a powerful passive way of probing properties of topological Josephson junctions. In particular, measurements of the Josephson emission enables to detect the expected presence of topological gapless Andreev bound states that give rise to emission at half the Josephson frequency f J , rather than conventional emission at f J . Here we report direct measurement of rf emission spectra on Josephson junctions made of HgTe-based gate-tunable topological weak links. The emission spectra exhibit a clear signal at half the Josephson frequency f J /2. The linewidths of emission lines indicate a coherence time of 0.3−4 ns for the f J /2 line, much shorter than for the f J line (3−4 ns). These observations strongly point towards the presence of topological gapless Andreev bound states, and pave the way for a future HgTe-based platform for topological quantum computation.

We analyze the current-biased Shapiro experiment in a Josephson junction formed by two one-dimensional nanowires featuring Majorana fermions. Ideally, these junctions are predicted to have an unconventional $4\pi$-periodic Josephson effect and thus only Shapiro steps at even multiples of the driving frequency. Taking additionally into account overlap between the Majorana fermions, due to the finite length of the wire, renders the Josephson junction conventional for any dc-experiments. We show that probing the current-phase relation in a current biased setup dynamically decouples the Majorana fermions. We find that besides the even integer Shapiro steps there are additional steps at odd and fractional values. However, different from the voltage biased case, the even steps dominate for a wide range of parameters even in the case of multiple modes thus giving a clear experimental signature of the presence of Majorana fermions.Comment: 5+10pages, 5+8 Figures, published in PRB (rapid

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Background: Cardiac amyloidosis (CA) is a serious though increasingly treatable cause of heart failure. Diagnosis is challenging and frequently unclear at echocardiography, which remains the most often used imaging tool. Objectives:We aimed to study the accuracy of a broad range of echocardiographic variables to develop multiparametric scores to diagnose CA in patients with proven light chain (AL) amyloidosis or those with increased heart wall thickness (IWT) in whom amyloid was suspected. We also aimed to further characterise structural and functional changes associated with amyloid infiltration. Methods:We studied 1187 consecutive patients evaluated at 3 referral centres for CA and analysed morphological, functional and strain-derived echo parameters with the aim of developing a score-based diagnostic algorithm. Cardiac amyloid burden was quantified using extracellular volume measurements at cardiac magnetic resonance.Results: 332 patients were diagnosed with AL amyloidosis and 339 patients with transthyretin (ATTR) CA. Concentric remodelling and strain-derived parameters displayed the best diagnostic performance. A multivariable logistic regression model incorporating relative wall thickness, E/e'ratio, longitudinal strain and tricuspid annular plane systolic excursion had greatest diagnostic performance in AL amyloidosis (area under the curve -AUC-0.90[95% confidence interval 0.87-0.92]), whilst addition of septal apical-to -base ratio yielded the best diagnostic accuracy in the IWT group (AUC 0.87[0.85-0.9]).Conclusions: Specific functional and structural parameters characterize different burdens of CA deposition with different diagnostic performances, and enable to define two scores that are sensitive and specific tools to diagnose or exclude CA.

No abstract

Cardiac angiosarcoma (CAS) is a rare malignant tumour whose genetic basis is unknown. Here we show, by whole-exome sequencing of a TP53-negative Li–Fraumeni-like (LFL) family including CAS cases, that a missense variant (p.R117C) in POT1 (protection of telomeres 1) gene is responsible for CAS. The same gene alteration is found in two other LFL families with CAS, supporting the causal effect of the identified mutation. We extend the analysis to TP53-negative LFL families with no CAS and find the same mutation in a breast AS family. The mutation is recently found once in 121,324 studied alleles in ExAC server but it is not described in any other database or found in 1,520 Spanish controls. In silico structural analysis suggests how the mutation disrupts POT1 structure. Functional and in vitro studies demonstrate that carriers of the mutation show reduced telomere-bound POT1 levels, abnormally long telomeres and increased telomere fragility.