Detection of the Copy Number Variants of Genes in Patients with Familial Cardiac Diseases by Massively Parallel Sequencing.

Introduction: The implication of copy number variations in familial heart disease is known, although in-depth knowledge is lacking; hence, more studies are needed to further our understanding. Massively parallel sequencing, thanks to its recent surge in use, is emerging as a valid tool for the detection of this type of variant, through the use of appropriate software.

Methods: We conducted a study with 182 patients diagnosed with mendelian cardiovascular diseases who underwent sequencing using a cardiac gene panel and then a specific calling process for copy number variations (CNVs) with ExomeDepth software, which provides us with a Bayes factor (BF), a score of the probability that a CNV detected is true.

Potential drug-drug interactions in COVID 19 patients in treatment with lopinavir/ritonavir.

Objectives: To determine the prevalence of potential interactions in COVID19 patients receiving lopinavir/ritonavir (LPV/r). The secondary objective was to develop recommendations and identify the risk factors associated with presenting potential interactions with LPV/r.

Subjects And Methods: Cross-sectional and multicenter study with the participation of 2 hospitals.

Potential drug-drug interactions in COVID 19 patients in treatment with lopinavir/ritonavir.

Objectives: To determine the prevalence of potential interactions in COVID-19 patients receiving lopinavir/ritonavir (LPV/r). The secondary objective was to develop recommendations and identify the risk factors associated with presenting potential interactions with LPV/r.

Subjects And Methods: Cross-sectional and multicenter study with the participation of 2 hospitals.

Sudden infant death as the most severe phenotype caused by genetic modulation in a family with atrial fibrillation.

Aims: To assess the functional impact of two combined KCNH2 variants involved in atrial fibrillation, syncope and sudden infant death syndrome.

Methods And Results: Genetic testing of a 4-month old SIDS victim identified a rare missense heterozygous in KCNH2 variant (V483I) and a missense homozygous polymorphism (K897T) which is often described as a genetic modifier. Electrophysiological characterisation of heterologous HERG channels representing two different KCNH2 genotypes within the family, showed significant differences in both voltage and time dependence of activation and inactivation with a global gain-of-function effect of mutant versus wild type channels and, also, differences between both types of recombinant channels.

Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood.

Objectives: Sudden unexplained death in children is a tragic and traumatic event, often worsened when the cause of death cannot be determined. This work aimed to investigate the presence of putative pathogenic genetic variants in a broad spectrum of cardiomyopathy, channelopathy and aortic disease associated genes that may have increased these children's vulnerability to sudden cardiac death.

Design: We performed molecular autopsy of 41 cases of sudden unexplained death in infants and children through massive parallel sequencing of up to 86 sudden cardiac death-related genes.

Next generation sequencing challenges in the analysis of cardiac sudden death due to arrhythmogenic disorders.

Inherited arrhythmogenic disorders is a relatively common cause of cardiac sudden death in young people. Diagnosis has been difficult so far due to the genetic heterogeneity of the disease. Next generation sequencing (NGS) is offering a new scenario for diagnosis.

Sarcomeric gene mutations in sudden infant death syndrome (SIDS).

In developed countries, sudden infant death syndrome (SIDS) represents the most prevalent cause of death in children between 1 month and 1 year of age. SIDS is a diagnosis of exclusion, a negative autopsy which requires the absence of structural organ disease. Although investigators have confirmed that a significant percentage of SIDS cases are actually channelopathies, no data have been made available as to whether other sudden cardiac death-associated diseases, such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of SIDS.

Prevalence of HCM and long QT syndrome mutations in young sudden cardiac death-related cases.

Cardiomyopathies and channelopathies are major causes of sudden cardiac death. The genetic study of these diseases is difficult because of their heterogenic nature not only in their genetic traits but also in their phenotypic expression. The purpose of the present study is the analysis of a wide spectrum of previously known genetic mutations in key genes related to hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), and Brugada syndrome (BrS) development.

Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by cardiac hypertrophy caused by mutations in sarcomere protein genes. MYBPC3 mutations are reported as a frequent cause of HCM. We aimed to identify the gene mutation underlying HCM in an Italian patient and his family composed of 13 relatives.

A new approach to long QT syndrome mutation detection by Sequenom MassARRAY system.

Congenital long QT syndrome is an inherited cardiac disorder characterized by a prolonged QT interval and polymorphic ventricular arrhythmias that could result in recurrent syncope, seizures or sudden death as the most dramatic event. Until now QT interval mutations have been described in 12 genes, where the majority of mutations reside in three genes KCNQ1, KCNH2, and SCN5A. Diagnosis and prognosis are directly related with the gene and mutation involved.