SCIENTIFIC BACKGROUND

CALM1, CALM2, CALM3, CASQ2, KCNJ2, RYR2, TECRL, TRDN

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal dominant inherited disease of the healthy cardiac muscle with an incidence of approximately 1:10,000. The arrythmias are adrenergically induced and manifest on average at the age of 8 years. Bi‑directional or polymorphic ventricular tachycardias are typical.

 

If left untreated, CPVT leads to syncope before the age of 40 in 60% of cases and to sudden cardiac death before the age of 30 in 30-50% of cases. The resting EKG seems normal. The earlier syncope occurs, the worse the prognosis, and the risk of cardiac events is about four times higher in men. The treatment is beta blockers. However, about 30% of patients remain symptomatic and may need an implanted defibrillator.

 

Pathogenic variants in the RYR2 gene (ryanodine type 2 receptor) can be identified in 40-70% of CPVT patients. This cardiac ryanodine receptor is the most important Ca2+releasing channel of the sarcoplasmic reticulum (SR) and plays a central role in the activation of cardiomyocytes. Rare variants in the CASQ2 (calsequestrin) and TECRL (trans-2,3-enoyl-CoA reductase-like) genes are detectable in about 3-5% of patients and lead to an autosomal recessive inherited form of CPVT. Variants in these 3 genes can cause a Ca2+ leakage current from the SR.

 

References

Roston et al. 2018, Europace 20:541 / Broendberg et al. 2017, Heart 103:901 / Devalla et al. 2016, EMBO Mol Med 8:1390 / Schulze-Bahr et al. 2015, Kardiologe DOI 10.1007/s12181-014-0636-2 / Roston et al. 2015, Circ Arrhythm Electrophysiol 8:633 / Van der Werf et al. 2012, Circ Arrhythm Electrophysiol 5:748 / Ackerman et al. 2011, Europace 13:1077 / Medeiros-Domingo et al. 2009, J Am Coll Cardiol 54:2065 / Marjamaa et al. 2009, BMC Medical Genetics 10:12 / Liu et al. 2008, Progr Cardiovasc Dis 51:23 / Priori et al. 2005, J Clin Invest 115:2033 / Postma et al. 2005, J Med Genet 42:863 / Priori et al. 2002, Circulation 106:69

GENES

CALM1, CALM2, CALM3, CASQ2, KCNJ2, RYR2, TECRL, TRDN
How to order

LATEST ARTICLES

Every year on April 25th, DNA Day celebrates the discovery of DNA’s double helix and the advances we’ve made in understanding genetics. D...

Read more

Neurodevelopmental disorders (NDDs) have diverse genetic origins, making diagnosis challenging. A new study analyzing over 1,100 pediatric patients f...

Read more

Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide, with a significant number of cases presenting at an advanced ...

Read more

Carrier screening is a genetic test designed to identify whether an individual carries a gene with changes (mutations) associated with inherited diso...

Read more

Trisomy 13, also known as Patau syndrome, is a genetic condition in which cells in the body have three copies of chromosome 13 instead of two. The co...

Read more

The human brain develops through a complex series of events, with genes carefully regulating the formation of neurons and glial cells. A recent study...

Read more

Rare diseases affect between 300 and 400 million people worldwide – more than cancer and AIDS combined [1, 2], but despite this, many people face a...

Read more

Rosalind Elsie Franklin was a brilliant and meticulous research scientist whose interdisciplinary work made fundamental contributions to various area...

Read more

February, designated as Cancer Awareness Month, marks a time to reflect on the remarkable progress made in cancer research and to inspire hope for th...

Read more

Introduction Cardiovascular disease (CVD) is a major health issue as it remains a leading cause of death worldwide [1]. CVD is responsible for mor...

Read more