Key result
Whole exome sequencing identified two novel heterozygous mutations (p.Phe142Leu and p.Asp96His) in the CALM3 gene in two pediatric patients with severe early-onset long QT syndrome.
Case Report (n=2)
No
The identification of novel CALM3 mutations in pediatric patients with severe early-onset LQTS supports the existence of a CALM3-specific calmodulinopathy and highlights the need to include CaM-encoding genes in genetic testing for young patients with severe LQTS.
Should not yet expand LQTS panels; hypothesis-generating for CALM3 calmodulinopathy.
The long QT syndrome (LQTS) is an inherited cardiac arrhythmia characterized by a prolonged heart rate–corrected QT interval (QTc) on the surface electrocardiogram (ECG). It is associated with syncope and sudden cardiac death from torsades de pointes, and is estimated to affect 1 per 2000 individuals.1 Fifteen genes have been implicated in familial LQTS, most of which encode cardiac ion channels or channel-interacting proteins.2 To date, mutations in the KCNQ1, KCNH2, and SCN5A genes (causing LQTS 1, 2, and 3) have been found in about 70% of cases, while mutations in other genes (LQTS 4–15) are found in only 5%, indicating that for ~25% of cases the genetic cause remains unknown.
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Chaix et al. (2016) conducted a case report in Long QT syndrome (n=2). CALM3 mutations (p.Phe142Leu and p.Asp96His) was evaluated on Identification of causal genetic variants. Whole exome sequencing identified two novel heterozygous mutations (p.Phe142Leu and p.Asp96His) in the CALM3 gene in two pediatric patients with severe early-onset long QT syndrome.
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