Related Experiment Video

Updated: Dec 29, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.3K

DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular

Krista Heliö1, Tiia Kangas-Kontio2, Sini Weckström3

  • 1Heart and Lung Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. krista.helio@helsinki.fi.

BMC Medical Genetics
|February 2, 2020
PubMed

Insights

Genetic variants in the desmoplakin (DSP) gene are linked to dilated cardiomyopathy (DCM), causing heart dysfunction and arrhythmias. This study found a specific DSP mutation in Finnish patients, revealing a low penetrance and potential links to myocardial inflammation.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Genetic Etiology of Cardiomyopathies

Background:

  • Dilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and systolic dysfunction.
  • Mutations in TTN and LMNA are major causes of familial DCM.
  • Desmoplakin (DSP) gene mutations, previously linked to ARVC, are increasingly associated with DCM.

Purpose of the Study:

  • To investigate the cardiac phenotype associated with a specific DSP gene mutation.
  • To identify the prevalence and clinical presentation of DSP-related DCM in Finnish patients.

Main Methods:

  • Next-generation sequencing to identify DSP mutations in ten unrelated Finnish index patients.
  • Sanger sequencing to confirm the variant in relatives.
  • Clinical evaluation and review of medical records.

Main Results:

  • A DSP c.6310delA, p.(Thr2104Glnfs*12) variant was identified in 17 individuals, with 11 (65%) meeting DCM criteria.
  • The variant caused left ventricular dilatation, dysfunction, and major ventricular arrhythmias.
  • Cardiac MRI revealed late gadolinium enhancement and myocardial edema in two patients, suggesting inflammation.

Conclusions:

  • DSP mutations in DCM patients can lead to an arrhythmogenic phenotype and sudden cardiac death (SCD) at a young age, supporting the concept of arrhythmogenic cardiomyopathy.
  • A truncating DSP variant showed relatively low penetrance in family members by age 40.
  • Further research is needed to explore the relationship between myocardial inflammation and pathogenic DSP variants.
Abstract

Keywords:
Arrhythmogenic cardiomyopathyCardiomyopathiesDSPDilated cardiomyopathyMutationdesmoplakin

More Related Videos

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

4.1K
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

14.1K

Related Concept Videos

Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
307
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
380
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
385
Cardiomyopathy I: Introduction and Classification01:25

Cardiomyopathy I: Introduction and Classification

Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
427
Mechanism of Cardiac Arrhythmias01:28

Mechanism of Cardiac Arrhythmias

Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
1.5K
ECG Interpretation of Arrhythmias II: Atrial, Junctional and Ventricular Arrhythmias01:25

ECG Interpretation of Arrhythmias II: Atrial, Junctional and Ventricular Arrhythmias

Arrhythmia is a condition characterized by an irregular heart rhythm, with ECG changes that differ based on its origin and nature. The types of arrhythmias discussed below include atrial, junctional, and ventricular arrhythmias.Atrial ArrhythmiasPremature Atrial Complexes (PACs): PACs are early atrial beats caused by stress, caffeine, alcohol, electrolyte imbalances, hypoxia, hyperthyroidism, or certain medications (e.g., bronchodilators and decongestants). The ECG shows early P waves with an...
377