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Your search keyword '"Nogue-Navarro L"' showing total 2 results
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2 results on '"Nogue-Navarro L"'

1. Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis

Author

Campuzano O, Sanchez-Molero O, Fernández A, Mademont-Soler I, Coll M, Perez-Serra A, Mates J, Del Olmo B, Pico F, Nogue-Navarro L, Sarquella-Brugada G, Iglesias A, Cesar S, Esther Carro Fernandez, Borondo JC, Brugada-Terradellas J, Castellà J, Medallo J, and Brugada R

Subjects
Rare Variant, Human Gene Mutation Database, Catecholaminergic Polymorphic Ventricular Tachycardia, Sudden Cardiac Death, Brugada Syndrome
Abstract

BACKGROUND: Sudden cardiac death is a natural and unexpected death that occurs within 1 h of the first symptom. Most sudden cardiac deaths occur during exercise, mostly as a result of myocardial infarction. After autopsy, some cases, especially in the young, are diagnosed as cardiomyopathies or remain without a conclusive cause of death. In both situations, genetic alterations may explain the arrhythmia. OBJECTIVE: Our aim was to identify a genetic predisposition to sudden cardiac death in a cohort of post-mortem cases of individuals who died during exercise, with a structurally normal heart, and were classified as arrhythmogenic death. METHODS: We analyzed a cohort of 52 post-mortem samples from individuals

Published
2017

2. Unpredicted Aberrant Splicing Products Identified in Postmortem Sudden Cardiac Death Samples.

Author

Coll M, Fernandez-Falgueras A, Iglesias A, Del Olmo B, Nogue-Navarro L, Simon A, Perez Serra A, Puigmule M, Lopez L, Pico F, Corona M, Vallverdu-Prats M, Tiron C, Campuzano O, Castella J, Brugada R, and Alcalde M

Subjects
Humans, Introns genetics, Exons genetics, Mutation, Protein Isoforms genetics, RNA Splice Sites genetics, RNA Splicing genetics, Death, Sudden, Cardiac etiology
Abstract

Molecular screening for pathogenic mutations in sudden cardiac death (SCD)-related genes is common practice for SCD cases. However, test results may lead to uncertainty because of the identification of variants of unknown significance (VUS) occurring in up to 70% of total identified variants due to a lack of experimental studies. Genetic variants affecting potential splice site variants are among the most difficult to interpret. The aim of this study was to examine rare intronic variants identified in the exonic flanking sequence to meet two main objectives: first, to validate that canonical intronic variants produce aberrant splicing; second, to determine whether rare intronic variants predicted as VUS may affect the splicing product. To achieve these objectives, 28 heart samples of cases of SCD carrying rare intronic variants were studied. Samples were analyzed using 85 SCD genes in custom panel sequencing. Our results showed that rare intronic variants affecting the most canonical splice sites displayed in 100% of cases that they would affect the splicing product, possibly causing aberrant isoforms. However, 25% of these cases (1/4) showed normal splicing, contradicting the in silico results. On the contrary, in silico results predicted an effect in 0% of cases, and experimental results showed >20% (3/14) unpredicted aberrant splicing. Thus, deep intron variants are likely predicted to not have an effect, which, based on our results, might be an underestimation of their effect and, therefore, of their pathogenicity classification and family members’ follow-up.

Published
2022
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