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.

The Role of Genetics in the Management of Heart Failure Patients.

Over the last decades, the relevance of genetics in cardiovascular diseases has expanded, especially in the context of cardiomyopathies. Its relevance extends to the management of patients diagnosed with heart failure (HF), given its capacity to provide invaluable insights into the etiology of cardiomyopathies and identify individuals at a heightened risk of poor outcomes. Notably, the identification of an etiological genetic variant necessitates a comprehensive evaluation of the family lineage of the affected patients.

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.

A Novel DLG1 Variant in a Family with Brugada Syndrome: Clinical Characteristics and In Silico Analysis.

Background: Brugada syndrome (BrS) is an inherited primary channelopathy syndrome associated to sudden cardiac death. Overall, variants have been identified in eighteen genes encoding for ion channel subunits and seven genes for regulatory proteins. Recently, a missense variant in DLG1 has been found within a BrS phenotype-positive patient.

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.

Prospective evaluation of pregnancy outcome in an Italian woman with late-onset combined homocystinuria and methylmalonic aciduria.

Background: Cobalamin metabolism disorders are rare, inherited diseases which cause megaloblastic anaemia and other clinical manifestations. Early diagnosis of these conditions is essential, in order to allow appropriate treatment as early as possible.

Case Presentation: Here we report the case of a patient who was apparently healthy until the age of 20, when she presented with impaired renal function and normocytic anaemia.

Use of Catridecacog in a patient with severe Factor XIII deficiency undergoing surgery.

Despite many articles regarding the antihemorrhagic treatment and prophylaxis, there is a lack of experience about how to best conduct major surgical procedures in patients with congenital factor XIII (FXIII) deficiency. Here we report a case of surgery (right inguinal hernia, complicated by heaviness and pain) performed in a patient with FXIII deficiency, receiving recombinant FXIII prophylaxis (Catridecacog 35 UI/kg every 28±2 days). Our experience shows that Catridecacog can be used safely and effectively not only for continued prophylaxis but also in surgery and adds to the very limited body of evidence currently available on surgery in this bleeding disorder.

Angiopoietin-1 haploinsufficiency affects the endothelial barrier and causes hereditary angioedema.

Background: Different mutations of the angiopoietin-1 gene (ANGPT1) have been associated with the occurrence of hereditary angioedema (HAE).

Objective: The purpose of the study is to clarify whether the ANGPT1 A119S variant plays its role via haploinsufficiency or a dominant negative effect.

Methods: The ability of ANGPT1 A119S variant to affect the endothelial barrier function was assessed by immunocytochemistry.

Double de novo mutations in dilated cardiomyopathy with cardiac arrest.

Here we report the identification of two novel mutations in a previously asymptomatic young man who suffered an out-of-hospital sudden cardiac arrest. During following evaluation, diagnosis of early stage dilated cardiomyopathy was established, while electrocardiogram monitoring showed frequent complex ventricular arrhythmias, incomplete right bundle branch block and prolonged QT duration. No reversible causes explaining the clinical presentation were established and an automatic implantable cardioverter defibrillator was therefore implanted.

Mutation of the angiopoietin-1 gene (ANGPT1) associates with a new type of hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare genetic disease usually caused by mutation in the C1 inhibitor or the coagulation Factor XII gene. However, in a series of patients with HAE, no causative variants have been described, and the pathophysiology of the disease remains unknown (hereditary angioedema with yet unknown genetic defect [U-HAE]). Identification of causative genes in patients with U-HAE is valuable for understanding the cause of the disease.

In vitro residual activity of phenylalanine hydroxylase variants and correlation with metabolic phenotypes in PKU.

Hyperphenylalaninemias (HPAs) are genetic diseases predominantly caused by a wide range of variants in the phenylalanine hydroxylase (PAH) gene. In vitro expression analysis of PAH variants offers the opportunity to elucidate the molecular mechanisms involved in HPAs and to clarify whether a disease-associated variant is genuinely pathogenic, while investigating the severity of a metabolic phenotype, and determining how a variant exerts its deleterious effects on the PAH enzyme. To study the effects of gene variants on PAH activity, we investigated eight variants: c.