A de novo ryanodine receptor 2 gene variant in a case of sudden cardiac death

  • Federica Foti
  • Fabio De-GiorgioEmail author
  • Giuseppe Vetrugno
  • Cristina Basso
  • Kalliopi Pilichou
Case Report


A 34-year-old man, who was previously fit and healthy, died suddenly on exercise. A post-mortem exam performed by forensic pathologists and a toxicological screening were normal; therefore, the cause of death was suspected to be sudden arrhythmic death syndrome, prompting the need for a molecular autopsy. Screening for genetic variations underlying arrhythmogenic genes by next-generation sequencing highlighted a heterozygous single-nucleotide variant in the exon n. 94 of the ryanodine receptor type 2 gene. This gene, encoding the cardiac ryanodine receptor, is one of the main genetic variants of catecholaminergic polymorphic ventricular tachycardia, estimated to affect 1 in 10,000 individuals. It manifests with syncope, seizures, or sudden death due to exercise- or emotional stress-induced bidirectional or polymorphic ventricular tachycardia, usually in children and young adults with morphologically normal hearts and normal baseline electrocardiograms. Even if this de novo missense mutation has not yet been associated with catecholaminergic polymorphic ventricular tachycardia, it is likely to be a disease-causing variant which leads to a defective protein responsible for disturbed ion flow.


Sudden arrhythmic death Molecular autopsy Next-generation sequencing Catecholaminergic polymorphic ventricular tachycardia Ryanodine receptor type 2 Post-mortem investigation 



Sudden arrhythmic death syndrome


Ryanodine receptor type 2


Catecholaminergic polymorphic ventricular tachycardia


Sarcoplasmic reticulum


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Federica Foti
    • 1
  • Fabio De-Giorgio
    • 1
    Email author
  • Giuseppe Vetrugno
    • 1
    • 2
  • Cristina Basso
    • 3
  • Kalliopi Pilichou
    • 3
  1. 1.Institute of Public Health, Section of Legal MedicineUniversità Cattolica del S. CuoreRomeItaly
  2. 2.Risk Management UnitFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
  3. 3.Cardiovascular Pathology Unit, Department of Cardiac-Thoracic-Vascular Sciences and Public HealthUniversity of PaduaPaduaItaly

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