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.

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.

Impaired control of the contact system in hereditary angioedema with normal C1-inhibitor.

Background: Hereditary angioedema (HAE) comprises HAE with C1-inhibitor deficiency (C1-INH-HAE) and HAE with normal C1-INH activity (nl-C1-INH-HAE), due to mutations in factor XII (FXII-HAE), plasminogen (PLG-HAE), angiopoietin 1 (ANGPT1-HAE), kininogen 1 genes (KNG1-HAE), or angioedema of unknown origin (U-HAE). The Italian network for C1-INH-HAE (ITACA) created a registry including different forms of angioedema without wheals.

Objective: We analyzed clinical and laboratory features of a cohort of Italian subjects with nl-C1-INH-HAE followed by ITACA to identify specific biomarkers.

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.