ECG of family members.

<p>(A) Twelve-lead ECG of index case. The ECG shows QTc of 500 ms. (B) Twelve-lead ECG of mother’s index case. The ECG shows a normal QTc, and (C) a LQT during tachycardia registered by Holter. (D) Twelve-lead ECG of brother’s index case. The ECG shows QTc of 485 ms.</p

Pedigree and electropherogram.

<p>(A) Index case is II.1. White round/squares indicate healthy status after clinical evaluation. Grey round/squares indicate LQTS after clinical evaluation. Plus sign indicates carrier of genetic variation. Minus sign indicates non-carrier of the genetic variation. (B) Electropherogram of the genetic variation identified (p.R20729G_<i>TTN</i>).</p

List of the 55 SCD-related genes included in our panel and its association with the disease.

<p>List of the 55 SCD-related genes included in our panel and its association with the disease.</p

NGS data showing CNV in the <i>KCNQ1</i> gene.

<p>(A) Coverage of all exons in the <i>KCNQ1</i> gene of several samples. (B) Detail coverage of exons 7 and 8 in several samples. (C) Normalized raw coverage of exons 7 and 8 showing a deletion in comparison to all other exons of the same gene. (D) In detail, normalized raw coverage of exons 7 and 8.</p

Large Genomic Imbalances in Brugada Syndrome (Part 2)

The last thirty-one pair of files of a sixty-three cohort of non-related patients of European descent with a definite BrS phenotype and negative genetic results (for Single Nucleotide Variants -SNVs- and small insertions/deletions -indels-

Influence of the phenotype on PPV discovery yield.

<p>Bar graph comparing the PPV detection yield in 8 different clinical categories (stated below the graph). Each bar shows the total number of patients for each clinical category divided in those with a PPV (black) and those without an identified PPV (white). The number of patients (in brackets) and percentages are given. Pos, positive; Neg, negative; Spont, spontaneous type 1 BrS ECG; Drug, drug-induced type 1 BrS ECG; <i>n</i>, number of patients.</p

Characteristics of the Spanish BrS patients carrying rare genetic variations.

<p>The table shows the clinical characteristics of the probands who carried rare genetic variations in <i>SCN5A</i>, <i>SCN2B</i>, or <i>RANGRF</i>. All of them are potentially pathogenic except that found in <i>RANGRF</i>, which is of unknown significance (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132888#sec014" target="_blank">discussion</a>). All the potentially pathogenic variations (PPVs) that had been previously reported, except p.P1725L and p.R1898C, had been identified in BrS patients. p.P1725L had been associated with Long QT Syndrome and p.R1898C was found in Exome Variant Server with a MAF of 0.0079%. No rare variations were identified in the control population. Patient’s age is expressed in years. Bold identifies the patients carrying variations that had not been described previously. M, male; F, female; S, syncope; ICD, intracardiac cardioverter defibrillator; UK, unknown; EPS, electrophysiological studies (+, positive response;-, negative response; N/P, not performed). The two patients who carried two PPVs each are identified by ^a and ^b, respectively.</p

Demographics of the 55 Spanish BrS patients included in the study.

<p>The table shows the demographic characteristics of all the patients included in the study. Numbers in parentheses represent the relative percentages for each condition. T1 ECG refers to Type 1 BrS diagnostic electrocardiogram (ECG), obtained either spontaneously, or after drug challenge. The information regarding both the electrophysiological studies (EPS) and the treatment was not available for all the patients. Two of the patients that didn’t receive any treatment died, and were not taken into account for the calculations of percentages (+2 dead). ICD, intracardiac cardioverter defibrillator.</p

Clinical data from the patient with the Copy Number Variant in <i>SCN5A</i>.

<p><b>A.</b> Basal electrocardiogram. <b>B.</b> Electrocardiogram after flecainide test, showing type I Brugada pattern. <b>C.</b> Family pedigree. The proband is indicated by an arrow. Subjects affected and unaffected by BrS are indicated by solid and open symbols, respectively. Genetic status for the <i>SCN5A</i> rearrangement is indicated by a superindex (+ or -).</p

Na_v1.5 channel scheme showing the relative position of the <i>SCN5A</i> PPVs identified in our cohort.

<p>Open symbols indicate already described variations and closed symbols locate novel variations reported in this study. DI to DIV designate the 4 domains of the protein, and numbers 1–6 identify the different segments within each domain. Crosses mark the voltage sensor.</p