Genetic Basis of Non Syndromic Congenital Diaphragmatic Hernia

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

— HCD GENE  

Official title:

Genetic Basis of Non Syndromic Congenital Diaphragmatic Hernia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02175264
• Other study ID #: CRC12074
• Status: Completed
• Phase: N/A
• First received: June 25, 2014
• Last updated: June 23, 2016
• Start date: June 2014
• Est. completion date: May 2016

Study information

• Verified date: June 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: May 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months and older

Eligibility

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

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hernia, Diaphragmatic
• Hernias, Diaphragmatic, Congenital
• Isolated Non Syndromic Left CDH With Postero Lateral Diaphragmatic Defect With Good Perinatal Outcome

Intervention

Genetic:
• Blood sample

Locations

Country	Name	City	State
France	Hopital béclère	Clamart

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	genes responsible for isolated CDH		One year	No
Secondary	prevalence of new identified genes in a cohort of CDH		One year	No