Isolated prolapse of the posterior mitral valve leaflet: phenotypic refinement, heritability and genetic etiology.

Background: Isolated posterior leaflet mitral valve prolapse (PostMVP), a common form of MVP, often referred as fibroelastic deficiency, is considered a degenerative disease. PostMVP patients are usually asymptomatic and often undiagnosed until chordal rupture. The present study aims to characterize familial PostMVP phenotype and familial recurrence, its genetic background, and the pathophysiological processes involved.

Filamin A heart valve disease as a genetic cause of inherited bicuspid and tricuspid aortic valve disease.

Objective: Variants in the gene have been associated with mitral valve dystrophy (MVD), and even polyvalvular disease has been reported. This study aimed to analyse the aortic valve and root involvement in -MVD families and its impact on outcomes.

Methods: 262 subjects (37 (18-53) years, 140 male, 79 carriers: +) from 4 -MVD families were included.

Heritable defects in telomere and mitotic function selectively predispose to sarcomas.

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls.

Multimodality imaging and transcriptomics to phenotype mitral valve dystrophy in a unique knock-in Filamin-A rat model.

Aims: Degenerative mitral valve dystrophy (MVD) leading to mitral valve prolapse is the most frequent form of MV disease, and there is currently no pharmacological treatment available. The limited understanding of the pathophysiological mechanisms leading to MVD limits our ability to identify therapeutic targets. This study aimed to reveal the main pathophysiological pathways involved in MVD via the multimodality imaging and transcriptomic analysis of the new and unique knock-in (KI) rat model for the FilaminA-P637Q (FlnA-P637Q) mutation associated-MVD.

Submerged membrane photobioreactor for the cultivation of Haslea ostrearia and the continuous extraction of extracellular marennine.

Haslea ostrearia is a marine diatom known to produce and excrete the marenine blue pigment. Its controlled, continuous and intensified cultivation remains a challenge. Thus, a submerged membrane photobioreactor (MPBR) was implemented in order to simultaneously and continuously cultivate H.

Generation of human induced pluripotent stem cell lines from three patients affected by Catecholaminergic Polymorphic ventricular tachycardia (CPVT) carrying heterozygous mutations in RYR2 gene.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is an exercise and emotional stress-induced life-threatening inherited heart rhythm disorder, characterized by an abnormal cellular calcium homeostasis. Most reported cases have been linked to mutations in the gene encoding the type 2 ryanodine receptor gene, RYR2. We generated induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear cells (PBMC) from three CPVT-affected patients, two of them carrying p.

Investigation of the photosynthetic response of Chlorella vulgaris to light changes in a torus-shape photobioreactor.

An efficient use of light is essential to achieve good performances in microalgae cultivation systems. This can be challenging particularly under solar conditions where light is highly dynamic (e.g.

Gap-134, a Connexin43 activator, prevents age-related development of ventricular fibrosis in Scn5a mice.

Down-regulation of Connexin43 (Cx43) has often been associated with the development of cardiac fibrosis. We showed previously that Scn5a heterozygous knockout mice (Scn5a), which mimic familial progressive cardiac conduction defect, exhibit an age-dependent decrease of Cx43 expression and phosphorylation concomitantly with activation of TGF-β pathway and fibrosis development in the myocardium between 45 and 60 weeks of age. The aim of this study was to investigate whether Gap-134 prevents Cx43 down-regulation with age and fibrosis development in Scn5a mice.

Effect of design dark fraction on the loss of biomass productivities in photobioreactors.

Design dark fraction reflects the unlit part of a microalgal culture system, as for example a hydraulic loop used for temperature or pH regulation, or a circulating pump for mixing purposes. This study investigates the impact of design dark fraction on photosynthetic biomass productivity of the eukaryotic microalgae Chlorella vulgaris. The effect of the volume of the dark fraction and the residence time spent in this dark fraction was investigated with two different nitrogen sources (N-NH, N-NO).

SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.

Aims: To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification.

Methods And Results: A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis.

Mental stress test: a rapid, simple, and efficient test to unmask long QT syndrome.

Aims: QT prolongation during mental stress test (MST) has been associated with familial idiopathic ventricular fibrillation. In long QT syndrome (LQTS), up to 30% of mutation carriers have normal QT duration. Our aim was to assess the QT response during MST, and its accuracy in the diagnosis of concealed LQTS.

Genetics of syndromic and non-syndromic mitral valve prolapse.

Mitral valve prolapse (MVP) is a common condition that affects 2%-3% of the general population. MVP is thought to include syndromic forms such as Marfan syndrome and non-syndromic MVP, which is the most frequent form. Myxomatous degeneration and fibroelastic deficiency (FED) are regarded as two different forms of non-syndromic MVP.

Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm.

Intracranial aneurysms (IAs) are acquired cerebrovascular abnormalities characterized by localized dilation and wall thinning in intracranial arteries, possibly leading to subarachnoid hemorrhage and severe outcome in case of rupture. Here, we identified one rare nonsense variant (c.1378A>T) in the last exon of ANGPTL6 (Angiopoietin-Like 6)-which encodes a circulating pro-angiogenic factor mainly secreted from the liver-shared by the four tested affected members of a large pedigree with multiple IA-affected case subjects.

New insights into mitral valve dystrophy: a Filamin-A genotype-phenotype and outcome study.

Aims: Filamin-A (FLNA) was identified as the first gene of non-syndromic mitral valve dystrophy (FLNA-MVD). We aimed to assess the phenotype of FLNA-MVD and its impact on prognosis.

Methods And Results: We investigated the disease in 246 subjects (72 mutated) from four FLNA-MVD families harbouring three different FLNA mutations.

Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation.

Background: Inherited cardiac conduction disease is a rare bradyarrhythmia associated with mutations in various genes that affect action potential propagation. It is often characterized by isolated conduction disturbance of the His-Purkinje system, but it is rarely described as a syndromic form.

Objectives: The authors sought to identify the genetic defect in families with a novel bradyarrhythmia syndrome associated with bone malformation.

Sodium-channel blocker challenge in the familial screening of Brugada syndrome: Safety and predictors of positivity.

Background: Sodium-channel blocker challenge (SCBC) is frequently performed to unmask Brugada syndrome.

Objective: We aim to identify predictors of positivity and complications of SCBC in the setting of familial screening of Brugada syndrome.

Methods: All consecutive patients from 2000 to 2014 who benefit from a sodium-channel blocker and belong to a family with at least 2 subjects affected by the syndrome were enrolled and followed prospectively.

The QUIDAM study: Hydroquinidine therapy for the management of Brugada syndrome patients at high arrhythmic risk.

Background: Although the implantable cardioverter-defibrillator (ICD) remains the main therapy for Brugada syndrome (BrS), it does not reduce life-threatening ventricular arrhythmia. Based on pathophysiologic mechanisms, hydroquinidine (HQ) has been suggested for effective prevention of arrhythmia.

Objective: The purpose of this study was to provide evidence-based data supporting HQ use to prevent life-threatening ventricular arrhythmia in high-risk patients with BrS.

Understanding the Pathophysiology of Intracranial Aneurysm: The ICAN Project.

Background: Understanding the pathophysiologic mechanism of intracranial aneurysm (IA) formation is a prerequisite to assess the potential risk of rupture. Nowadays, there are neither reliable biomarkers nor diagnostic tools to predict the formation or the evolution of IA. Increasing evidence suggests a genetic component of IA but genetics studies have failed to identify genetic variation causally related to IA.

Brugada syndrome: Diagnosis, risk stratification and management.

Brugada syndrome is a rare inherited arrhythmia syndrome leading to an increased risk of sudden cardiac death, despite a structurally normal heart. Diagnosis is based on a specific electrocardiogram pattern, observed either spontaneously or during a sodium channel blocker test. Among affected patients, risk stratification remains a challenge, despite recent insights from large population cohorts.