Genotype/Phenotype Relationship in a Consanguineal Family With Brugada Syndrome Harboring the R1632C Missense Variant in the SCN5A Gene

Figures

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  Figure 1. Electrocardiograms of proband and family members at baseline and after ajmaline challenge. Proband’s father (II-7), proband (III-3), and proband’s youngest sister (III-6) exhibit the BrS type 1 pattern after ajmaline administration, confirming the BrS diagnosis. Proband’s second eldest sister (III-2) and brothers (III-4 and III-5) are ajmaline negative.

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  Figure 2. Arrhythmogenic substrate characterization in Proband and Father. Electrocardiogram (left) demonstrates the type 1 BrS pattern after ajmaline administration, confirming the diagnosis. Potential duration map after ajmaline infusion (center) reveals the full extent of the arrhythmogenic substrate. The area of the substrate exhibiting potential durations at least 160 ms in duration is denoted by the “marked area” and is 13.7 cm2 for Proband and 16.6 cm2 for Proband’s father. The duration of fragmented potentials (right) were prolonged and measured 272 ms for Proband and 325 ms for Proband’s father.

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  Figure 3. Identification of the c. 4894C>T (p.Arg1632CyS) missense mutation in the SCN5A gene. NGS paired-end reads loaded in the IGV genome browser. The arrow indicates the position of the single nucleotide variation in SCN5A gene in the proband (A) compared to a wild type control sample (B). SCN5A gene is in the reverse orientation on the chromosome. Sanger sequencing electropherogram confirm the presence of the variants in the proband (C) and the absence in a wild type control (D).

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  Figure 4. Family pedigree. Proband identified with arrow. Square: male; circle: female; slash: deceased; grayed: clinically affected by Brugada syndrome; star: molecularly confirmed SCN5A variant; star with slash: genetic test for SCN5A variant performed but negative.