Investigation of a Large Kindred Reveals Cardiac Calsequestrin () as a Cause of Brugada Syndrome.

Background: Brugada syndrome (BrS) is an inherited primary channelopathy syndrome associated with the risk of ventricular fibrillation (VF) and sudden cardiac death in a structurally normal heart.

Aim Of The Study: The aim of this study was to clinically and genetically evaluate a large family with severe autosomal dominant Brugada syndrome.

Methods: Clinical and genetic studies were performed.

DAB2IP associates with hereditary angioedema: Insights into the role of VEGF signaling in HAE pathophysiology.

Background: In the recent years, there was an important improvement in the understanding of the pathogenesis of hereditary angioedema (HAE). Notwithstanding, in a large portion of patients with unknown mutation (HAE-UNK) the genetic cause remains to be identified.

Objectives: To identify new genetic targets associated with HAE, a large Argentine family with HAE-UNK spanning 3 generations was studied.

Homozygous MTHFR C677T carriers develop idiopathic portal vein thrombosis 20 years earlier than wild type.

The aim of this study was to evaluate the impact of methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C→T667 transition) on age at first idiopathic portal vein thrombosis (PVT) and to identify clinical and/or laboratory variables influencing age at first PVT, including plasma homocysteine and the prothrombin rs1799963 PT (G→A transition at position 20210) (PT) mutation. A retrospective cross-sectional cohort, including 15 MTHFR TT, 32 MTHFR TC and 22 MTHFR CC idiopathic PVT participants contributing demographics, age at PVT, plasma concentrations of homocysteine and of natural anticoagulants. MTHFR TT carriers presented with a lower age at PVT than heterozygous or wild-type genotypes (31 ± 8 vs.

Homozygous MTHFR C667T carriers ≤45 years old develop central retinal vein occlusion five years earlier than wild type.

Purpose: To assess age at 1 central retinal vein occlusion (CRVO) in carriers ≤ 45 years old of the methylenetetrahydrofolate reductase (MTHFR) C667T genotype compared to heterozygous and wild type, and to identify predictors of age at CRVO.

Methods: Retrospective cohort study consisting of 18 MTHFR TT, 23 MTHFR TC and 28 MTHFR CC participants; information regarding age, sex, age at CRVO, history of dyslipidaemia, hypertension, smoking and plasma HC measured by immunoassay were collected.

Results: Age at CRVO was lower in MTHFR TT than MTHFR TC and CC (32 ± 6 vs 38 ± 5 vs 37 ± 6 years, respectively,  = 0.

A Novel Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis.

Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern.

Liver Cirrhosis Patients Homozygous for MTHFR C677T Develop Portal Vein Thrombosis 8 Years Earlier Than Wild Type.

Background And Aim: Age at portal vein thrombosis (PVT) in liver cirrhosis (LC) carriers of the methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C → T667 transition) polymorphism has never been addressed; we compared age at PVT in LC patients genotyped for the MTHFR and explored the interrelated clinical and laboratory factors predicting age at PVT.

Approach And Results: Retrospective cross-sectional cohort study. PVT participants: MTHFR CC n = 36, MTHFR CT n = 53, MTHFR TT n = 19; age, sex, age at PVT, Child-Pugh score, rs1799963 PT polymorphisms (G → A 20,210 transition), plasma HC and natural anticoagulants available for all participants.

Juvenile patients with the homozygous MTHFR C677T genotype develop ischemic stroke 5 years earlier than wild type.

To compare age at 1st ischaemic stroke (IS) in a cohort of juvenile (< 46 years of age) IS patients evaluated for the rs1801133 polymorphism (C → T677) of the methylene tetrahydrofolate reductase (MTHFR) gene; to identify predictors of age at IS and of type of cerebral vessel involvement, small vessel disease (SVD) vs large vessel disease (LVD) responsible for the IS; to evaluate possible associations between other clinical and laboratory variables. Retrospective cohort study on 82 MTHFR TT, 54 MTHFR TC and 34 MTHFR CC participants; data regarding age, sex, age at IS, history of dyslipidaemia, hypertension, smoking, migraine and homocysteine (HC) as well as neuroimaging were collected. Age at IS was lower in MTHFR TT than MTHFR TC and CC (35 ± 4 vs 38 ± 0 vs 40 ± 3 years, respectively, p = 0.

Associations Between Personality Traits, Perceived Stress and Depressive Symptoms in Gynecological Cancer Patients Characterized by the Short and Long Allele Variant of the 5-HTTLPR Genotype: Preliminary Results.

Objective: The study explored associations between personality traits, perceived stress and symptoms of depression in oncological patients characterized by the two variants of the serotonin transporter (5-HTTLPR) polymorphisms.

Method: The sample was composed of 41 gynecological cancer patients who completed self-reported questionnaires including the NEO Five-Factor Inventory, the dimension of depression-dejection (D/D) of the Profile of Moods State and the Perceived Stress Scale (PSS). The polymerase chain reaction was also employed to identify genotypes in the serotonin (5HTT) polymorphism.

Earlier onset of peripheral arterial thrombosis in homozygous MTHFR C677T carriers than in other MTHFR genotypes: a cohort study.

To investigate whether age at first presentation of pure peripheral arterial thrombosis (PAT) in lower and upper limbs and in the splanchnic circulation occurs earlier in carriers of the methylenetetrahydrofolate reductase (MTHFR) T677T genotype compared to the heterozygous and wild type and to identify predictors of a possible earlier onset. Retrospective cohort study on 27 MTHFR TT, 29 MTHFR TC and 29 MTHFR CC participants; data regarding age, sex, age at PAT, clinical history (dyslipidaemia, hypertension, smoking, obesity) and homocysteine (HC) measured by immunoassay were collected. Age at PAT was lower in MTHFR TT than MTHFR TC and CC (43 ± 9 vs 47 ± 9 vs 51 ± 4 years, respectively, p = 0.

Psychosomatic syndromes are associated with IL-6 pro-inflammatory cytokine in heart failure patients.

Psychosomatic syndromes have emerged as an important source of comorbidity in cardiac patients and have been associated with increased risk for adverse outcomes in patients with heart failure (HF). Understanding of the mechanisms underlying this connection is limited, however immune activity represents a possible pathway. While there have been numerous studies connecting immune activity to psychosomatic psychopathology, there is a lack of research on patients with HF.

Pathogenic Variant (1085G>A) Linked to Infantile Progressive Neurological Disorder: Evidence of Maternal Transmission by Germline Mosaicism and Influence of a Contemporary in cis Variant (1535T>C).

Mitochondria are dynamic organelles undergoing continuous fusion and fission with Drp1, encoded by the gene, required for mitochondrial fragmentation. dominant pathogenic variants lead to progressive neurological disorders with early exitus. Herein we report on the case of a boy affected by epileptic encephalopathy carrying two heterozygous variants () of the gene: a pathogenic variant (PV) c.

Rare Defects: Looking at the Dark Face of the Thrombosis.

Venous thromboembolism (VTE) constitutes a serious and potentially fatal disease, often complicated by pulmonary embolism and is associated with inherited or acquired factors risk. A series of risk factors are known to predispose to venous thrombosis, and these include mutations in the genes that encode anticoagulant proteins as antithrombin, protein C and protein S, and variants in genes that encode instead pro-coagulant factors as factor V (FV Leiden) and factor II (FII G20210A). However, the molecular causes responsible for thrombotic events in some individuals with evident inherited thrombosis remain unknown.

Homozygous methylentetrahydrofolate reductase C667T genotype anticipates age at venous thromboembolism by one decade.

The aim of the study was to compare age at first venous thromboembolism (VTE), plasma homocysteine and activated partial thromboplastin time ratio (aPTTr) amongst unprovoked VTE patients with the methylentetrahydrofolate reductase (MTHFR) C667T genotypes, and to identify predictors of age at first VTE, of plasma homocysteine and of the aPTTr; to evaluate whether heterozygous or homozygous prothrombin (PT) G20210A mutation lowered the age at first VTE when associated with MTHFR TT. Retrospective cohort study on 259 MTHFR TT, 76 MTHFR TC and 64 MTHFR CC participants with unprovoked VTE; each participant contributed age, sex, age at VTE, history of dyslipidaemia, hypertension, smoking, homocysteine (measured by enzyme immunoassay) and aPTTr (measured by standard coagulation assay). Age at first VTE was lower in MTHFR TT than MTHFR TC and CC (41 ± 14 vs.

The Genetics of Hereditary Angioedema: A Review.

Hereditary angioedema is a rare inherited disorder characterized by recurrent episodes of the accumulation of fluids outside of the blood vessels, causing rapid swelling of tissues in the hands, feet, limbs, face, intestinal tract, or airway. Mutations in SERPING1, the gene that encodes C1-INH (C1 esterase inhibitor), are responsible for the majority of cases of hereditary angioedema. C1 esterase inhibitor (C1-INH) is a major regulator of critical enzymes that are implicated in the cascades of bradykinin generation, which increases the vascular permeability and allows the flow of fluids into the extracellular space and results in angioedema.

Anticoagulation in Italian patients with venous thromboembolism and thrombophilic alterations: findings from START2 register study.

Background: Randomised control trials have assessed the efficacy and safety of direct oral anticoagulants in the prophylaxis and treatment of venous thromboembolism (VTE). Positive but limited results have been reported in patients with inherited thrombophilia. Using an Italian, multicentre, prospective registry of consecutive patients presenting with symptomatic, acute VTE, we aimed to assess which factors are involved in making the choice of the drug that best fits the patient's risk profile in a large real-world setting of VTE patients.

Maladaptive Coping Strategies and Neuroticism Mediate the Relationship Between 5HTT-LPR Polymorphisms and Symptoms of Anxiety in Elite Athletes.

Objective: Previous studies have suggested that genetic factors, personality traits and coping strategies might play both independent and interacting roles when influencing stress-related anxiety symptoms. The aim of this study was to examine whether Neuroticism and maladaptive coping strategies mediate the association between the serotonin transporter gene-linked polymorphic region (5HTT-LPR) and symptoms of anxiety and depression in elite athletes who experience high levels of competitive stress.

Method: One hundred and thirty-three participants were genotyped for the 5-HTTLPR polymorphism and then asked to complete the Cope Orientation to Problems Experienced Inventory and the NEO Five-Factor Inventory.

Predictive Value of Oxidized Low-Density Lipoprotein/β-Glycoprotein-I Complexes (oxLDL/βGPI) in Nonautoimmune Atherothrombosis.

Introduction: Lipid oxidation is a definite feature of atherosclerosis, and oxidized low-density lipoprotein (oxLDL) is not only highly immunogenic but toxic to several cell types. Beta-2-glycoprotein-I (βGPI) dampens oxLDL toxicity by forming binary oxLDL/βGPI complexes. We evaluated whether circulating oxLDL/βGPI complexes are associated to atherosclerosis-related events (ARE) and to venous thromboembolism (VTE).

Preliminary Data From the Study of Coagulative Profile of HIV Infected Individuals Suggest a Role For Point Mutations in the Gene in Protein S Deficiency in Individuals Undergoing Highly Antiretroviral Therapy.

Background: HIV infection is a known prothrombotic condition but factors involved are still controversial. A role for antiretrovirals, especially protease inhibitors, was advocated.

Objectives: The study aimed to analyze the levels of anticoagulant proteins in virally suppressed HIV-infected subjects treated with different anti-retroviral regimens.

Factor XI gene variants in factor XI-deficient patients of Southern Italy: identification of a novel mutation and genotype-phenotype relationship.

Congenital Factor XI (FXI) deficiency shows a high variability in clinical phenotype. To date, many allele variants have been shown to cause this bleeding disorder. However, the genotype-phenotype relationship is difficult to establish.