Genetic Basis of Non Syndromic Congenital Diaphragmatic Hernia

NCT ID: NCT02175264

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 73 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2016-05-31

Brief Summary

In isolated congenital diaphragmatic hernia (CDH), recurrent risk is low suggesting the occurrence of novo mutations (dominant or recessive). Our objective is to test this hypothesis by combining the search for pathogenic genomic alteration and intragenic mutations through whole exome sequencing in a homogenous group of patients.

Detailed Description

To elucidate the genetic basis of non syndromic congenital diaphragmatic hernia in a sub group of individuals with similar phenotype: Isolated CDH presenting with postero-lateral-left diaphragmatic defect with good perinatal outcome (n=16) To establish the prevalence of the identified gene(s) in a cohort of identical patients (n=30)

Two complementary approaches will be used:

• Search for pathogenic genomic alterations using microarrays (~2.106 markers (SNP and CNV) in 16 trios (affected child and 2 parents).
• Sequencing of the whole exome from patient genomic DNA (n=16)
• Selection of unknown or very rare variants according to different criteria: recessive or dominant model, prediction of their pathogenicity, filtered on genes already known in CDH or involved in diaphragmatic development and non annotated CNV or variants of new gene(s) shared by different patients.
• Variants will be validated by Sanger sequencing (for intragenic variants) or quantitative PCR (for CNV) on CDH cases and their parents as well as their absence on 100 controls.

Conditions

Isolated Non Syndromic Left CDH With Postero Lateral Diaphragmatic Defect With Good Perinatal Outcome

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients and Families with isolated non syndromic CDH cases

Blood sample

Intervention Type: GENETIC

Interventions

Blood sample

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Families with one (or more) non syndromic CDH child
• Signed consent form

Exclusion Criteria

• Syndromic CDH or associated with a known karyotype anomaly
• No signed consent form
• Not affiliated to French social security

• Minimum Eligible Age: 3 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Melki, MD-PHD

Role: STUDY_DIRECTOR

Institut National de la Santé Et de la Recherche Médicale, France

Locations

Hopital béclère

Clamart, , France

Countries

France

Other Identifiers

CRC12074

Identifier Type: -

Identifier Source: org_study_id