Catecholaminergic polymorphic ventricular tachycardia (and seizure) caused by a novel homozygous likely pathogenic variant in CASQ2 gene

Background: Although structural heart disease is frequently present among patients who experience sudden cardiac death (SCD), inherited arrhythmia syndromes can also play an important role in the occurrence of SCD. CPVT2, which is the second-most prevalent form of CPVT, arises from an abnormality in the CASQ2 gene. Objective: We represent a novel CASQ2 variant that causes CPVT2 and conduct a comprehensive review on this topic.Methods: The proband underwent Whole-exome sequencing (WES) in order to ascertain the etiology of CPVT. Subsequently, the process of segregating the available family members was carried out through the utilization of PCR and Sanger Sequencing. We searched the google scholar and PubMed/Medline for studies reporting CASQ2 variants, published up to May 10,2023. We used the following mesh term Calsequestrin and using free-text method with terms including CASQ2,CASQ2 variants, and CASQ2 mutation.Results: The CASQ2 gene was found to contain an autosomal recessive nonsense variant c.268_269insTA:p. Gly90ValfsTer4, which was identified by WES. This variant was determined to be the most probable cause of CPVT in the pedigree under investigation. Conclusion: CASQ2 variants play an important role in pathogenesis of CPVT2. Notabely, based on results of our study and other findings in the literature the variant in this gene may cause an neurological signs in the patients with CPVT2. Further studies are needed for more details about the role of this gene in CPVT evaluation, diagnosis, and gene therapy.

Automated summary

This study presents a novel CASQ2 variant that causes CPVT2 and provides a comprehensive review on this topic. The findings suggest that CASQ2 variants play an important role in the pathogenesis of CPVT2 and may be associated with neurological symptoms in patients. Further studies are needed to explore the specific role of this gene in CPVT evaluation, diagnosis, and gene therapy.