Heart Defects, Congenital
Conditions
Keywords
Congenital heart disease, Ventriculo-arterial discordance, Transposition of the great arteries, Transposition congenitally corrected of the great arteries, Genetic, Whole genome sequencing
Brief summary
Number of centres planned : 16 centres in France Type of study / Study design : Research Involving the Human Person category 2. Multicentric. Prospective Planning of the study : Total duration: 57,5 months. Recruitment period: 33.5 months. Follow-up time per patients : 2 years Expected number of cases : The study will involve a maximum of 900 individuals, from 16 centers in France300 family trios (consisting of 150 index cases and their 2 parents, healthy volunteers, N= 450 individuals) \- In the event of unavailability, refusal, non-compliance with an inclusion or exclusion criterion concerning one of the biological parents, only the index case (patient) will be included in the study without his or her parents. The 300 index cases with ventriculo-arterial discordance will be divided into two groups: 100 double discordance cases and 200 large-vessel transpositions. These group inclusion targets are theoretical. If the proportion of patients available for inclusion turns out to be higher than expected for one of the groups, the targets may be adjusted, while maintaining a maximum of 300 cases included (corresponding to 900 subjects if all trios are complete). Patients and their parents will be informed of the study by their referring cardiologist, and their written consent will be obtained. Translated with DeepL.com (free version) Treatment, procedure, combination of procedures under consideration : * Blood samples for genetic analyses collected at the inclusion visit for patients and parents in case of trio families Schedule of different visits and examinations : Inclusion visit: * Collection of demographic, clinical data from the index case and parents * DNA sampling for genetic research (biocollection) of the index case or family trio * Completion of the quality of life questionnaire Annual visit with a 2 years follow-up: * Retrieval of data from the index case * Completion of the quality of life questionnaire
Interventions
BIOLOGICALGenetic analyses: whole genome sequencing
Identification of de novo genetic variants using a whole genome sequencing (WGS) approach in the context of familial trios analysis
Sponsors
Inserm UMR1087, CNRS UMR6291
Clinique des Données, CIC 1413, CHU Nantes
CIC-FEA, CIC 1413, CHU Nantes
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
900 participants (300 trio families)
Eligibility
Sex/Gender
ALL
Age
1 Minutes to 100 Years
Healthy volunteers
No
Inclusion criteria
* Patients with transposition of the great arteries or transposition congenitally corrected of the great arteries with healthy parents and no family history of congenital heart disease (familial trio) * Or patients with transposition of the great arteries or transposition congenitally corrected of the great arteries with or without a history of congenital heart disease (familial form or sporadic case) * Affiliated or beneficiaries of a social security scheme or similar * After obtaining oral consent from patients and/or parents if applicable Parents (for family trios) : \- Biological parents of the child included in the PRECIPED study
Exclusion criteria
* Patients with transposition of the great arteries or transposition congenitally corrected of the great arteries with hypoplastic ventricle or atrioventricular and/or ventriculoarterial valve atresia * Patient with an identified malformation syndrome * Patients under guardianship/curatorship * Patients with State Medical Aid * Refusal of consent by the patient and/or one of the two parents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification new genes/variants involved in congenital heart disease with transposition congenitally corrected of the great arteries, based on whole genome sequencing of familial trios. | 24 months | Identification of de novo genetic variants using a whole genome sequencing (WGS) approach in the context of familial trios analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation the diagnostic contribution of parental cardiovascular screening in case of ventriculo-arterial discordance (transposition of the great arteries, transposition congenitally corrected of the great arteries) in the index case. | 24 months | Evolution of diagnostic performance for congenital heart disease in relatives of the index case with ventriculo-arterial discordance following the introduction of parental screening. |
| Identification new familial forms of ventriculo-arterial discordance. | 24 months | Identification of genotype/phenotype relationships by studying associations between clinical features and identified genetic variants. |
| Identification epigenetic modifications by analysis of the epigenome of sporadic forms when genome sequencing is not contributory. | 24 months | Detection of epigenetic modifications. |
| Identification allelic variants associated with prognosis and/or response to treatment, with the aim of eventually developing a precision medicine programme in paediatric cardiology | 2 years | Identification of genotype/phenotype relationships in relation to prognosis and/or response to treatment |
| Assessing the quality of life of patients with ventriculo-arterial discordance as well as their parents | 2 years | To document quality of life longitudinally in this patient population using Pediatric Quality of Life InventoryTM (scale from 0 to 4 ; 4 being the worst outcome) |
Countries
France
Outcome results
None listed