Genetic Basis of Non Syndromic Congenital Diaphragmatic Hernia

Completed

• Conditions: Isolated Non Syndromic Left CDH With Postero Lateral Diaphragmatic Defect With Good Perinatal Outcome
• Interventions: Genetic: Blood sample

• Registration Number: NCT02175264
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-06-25
• Study First Submitted QC: 2014-06-25
• Study First Posted: 2014-06-26
• Primary Completion: 2016-02
• Study Completion: 2016-05
• Status Verified: 2016-06
• Last Update Submitted: 2016-06-23
• Last Update Posted: 2016-06-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 73

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients and Families with isolated non syndromic CDH cases	Blood sample	-

Primary Outcome Measures

Name	Time	Method
genes responsible for isolated CDH	One year

Secondary Outcome Measures

Name	Time	Method
prevalence of new identified genes in a cohort of CDH	One year

Trial Locations

Locations (1)

Hopital béclère; 🇫🇷 Clamart, France