Identification of Genetic Basis of Atrioventricular Conduction Defects: From Congenital Forms to Degenerative Forms

Nantes University Hospital (NUH)

Status: Unknown

Conditions: Cardiac Conduction Defect Progressive; Congenital Complete Heart Block

Treatments: Genetic: genetic blood analysis

Study type: Observational

Funder types: Other

Identifiers

NCT02881671

PROG/11/33

Details and patient eligibility

About

Identification of genes involved in congenital atrioventricular block and progressive Cardiac Conduction Disease.

Full description

Atrioventricular blocks are a heterogenous group of diseases involving children with congenital atrioventricular block (CAB) and more frequently elderly patients affected by progressive Cardiac Conduction Disease (PCCD).

The aim of the study is to uncover the genetic model, likely more complex than previously appreciated, and characterize the gene expression remodelling leading to high degree of conduction defect.

The recent technological developments in genomics coupled to the availability of large and highly characterized biobanks of patients have now set the stage:

1. To identify rare genetic variants/new genes contributing to CAB and PCCD by exome sequencing on familial form suspected to impact strongly the phenotype
2. To identify common genetic variants modulating the risk of developing (severe) PCCD by GWAS
3. To estimate the prevalence and relevance of genes uncovered by TASK#1, #2 in large patient sets (PCCD and CAB) by NGS.

Enrollment: 2,600 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Congenital atrioventricular block inclusion criteria:

• Patients with idiopathic congenital atrioventricular block diagnosed before the age of 15 years.
• Non-immune congenital atrioventricular block documented by a maternal serology (negative for anti-nuclear antibodies or anti Ro-SSA antibodies and anti La-SSB antibodies)
• Written consent to participate to the study and written consent of both parents.
• Parents of children with idiopathic congenital atrioventricular block.

Congenital atrioventricular block exclusion criteria

• Positive maternal serology
• Patients or parents who are unable to sign or who refuse to sign an informed consent

Progressive Cardiac Conduction Disease inclusion criteria

• Patients with isolated cardiac conduction disorder with a normal morphology of the heart confirmed by echocardiography.
• Relatives of patients with isolated cardiac conduction disorder
• Written consent to participate to the study

Progressive Cardiac Conduction Disease exclusion criteria

• Patients with cardiac conduction disorder associated with a structural cardiopathy or due to an identified cause
• Patients who are unable to sign or who refuse to sign an informed consent

Trial design

2,600 participants in 4 patient groups

Patients with congenital atrioventricular block

Description:

Patient with congenital atrioventricular block

Treatment:

Genetic: genetic blood analysis

relatives with congenital atrioventricular block

Description:

Normal relatives of patients with congenital atrioventricular block

Treatment:

Genetic: genetic blood analysis

Patients with progressive Cardiac Conduction Disease

Description:

Patients with progressive Cardiac Conduction Disease,

Treatment:

Genetic: genetic blood analysis

relatives with progressive Cardiac Conduction disesae

Description:

Normal relatives of patients with progressive Cardiac Conduction Disease

Treatment:

Genetic: genetic blood analysis