Key result
A novel heterozygous missense mutation (p.Glu25Gly) in the N-terminal domain of the SCN5A gene co-segregated with dilated cardiomyopathy and sudden cardiac arrest within a family.
Why the study?
Dilated cardiomyopathy has significant morbidity and mortality, with familial transmission reported in 20-35% of cases highlighting the role of genetics in this disorder.
Is the novel SCN5A c.74A > G mutation associated with familial dilated cardiomyopathy and sudden cardiac arrest?
Case Report
Is the novel SCN5A c.74A > G mutation associated with familial dilated cardiomyopathy and sudden cardiac arrest?
This study provides the first evidence associating a variant in the N-terminal domain of SCN5A with familial dilated cardiomyopathy and sudden cardiac arrest.
Suggests SCN5A variants in familial DCM with SCA; hypothesis-generating and should not yet change practice.
Dilated cardiomyopathy (DCM) has significant morbidity and mortality. Familial transmission is reported in 20–35% of cases, highlighting the role of genetics in this disorder. We present an interesting family in which the index case is a 64-year-old woman who survived a sudden cardiac arrest. She presented left ventricular dilatation and dysfunction, which indicated the presence of DCM, as well as a history of DCM and sudden arrest in her family (mother and sister). Genetic testing identified a heterozygous mutation c.74A > G missense change that causes an amino acid, p.Glu25Gly, change in the N-terminal domain of the SCN5A protein. After performing an exhaustive family medical history, we found that this previously not described mutation segregated within the family. All relatives with the DCM phenotype were carriers, whereas none of the noncarriers showed signs of heart disease, so this mutation is the most likely cause of the disease. This is the first time that a variant in the N-terminal domain of SCN5A has been associated with DCM.
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Rico et al. (2021) conducted a case report in Familial Dilated Cardiomyopathy and Sudden Cardiac Arrest. SCN5A mutation (c.74A > G, p.Glu25Gly) vs. Noncarrier family members was evaluated on Dilated cardiomyopathy phenotype. A novel heterozygous missense mutation (p.Glu25Gly) in the N-terminal domain of the SCN5A gene co-segregated with dilated cardiomyopathy and sudden cardiac arrest within a family.
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