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

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

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

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.

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