Novel variants in TECRL leading to catecholaminergic polymorphic ventricular tachycardia

Area of Science:

• Genetics
• Cardiology
• Molecular Biology

Background:

• Recessive variants in the TECRL gene are linked to catecholaminergic polymorphic ventricular tachycardia 3 (CPVT3), a condition characterized by prolonged QT intervals.
• CPVT3 can lead to life-threatening cardiac events, even in previously healthy individuals.

Purpose of the Study:

• To report a case of cardiac arrest in an adolescent male.
• To identify the genetic cause of the cardiac event using rapid whole-genome sequencing.
• To characterize novel variants in the TECRL gene associated with the patient's condition.

Main Methods:

• Whole-genome sequencing was performed rapidly to identify genetic variants.
• Analysis focused on identifying pathogenic or likely pathogenic variants in genes associated with cardiac arrhythmias.
• Segregation analysis was performed to determine the inheritance pattern of identified variants.

Main Results:

• A novel, maternally inherited likely pathogenic variant (c.915T>G [p.Tyr305Ter]) in the TECRL gene was identified.
• An additional de novo 19-kb duplication encompassing multiple exons of TECRL (chr4:65165944-65185287, dup [4q13.1]) was detected.
• These genetic findings provided a diagnosis for the patient's cardiac arrest.

Conclusions:

• Rapid whole-genome sequencing is crucial for timely diagnosis and management of genetic cardiac conditions like CPVT3.
• The identified novel TECRL variants, including a duplication, expand the known mutational spectrum for TECRL-associated CPVT3.
• This case highlights the importance of comprehensive genetic analysis in unexplained cardiac events.