Search for New Genetic Mutations Major Effect in Crohn's Disease

Study Overview
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Brief Summary
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This study highlight genetics mutations with major effect in Crohn's Disease (CD) by WES in individuals affected and healthy individuals from EPIMAD Inserm InVS registry families.

Detailed Description
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The EPIMAD Registry covers a large area of Northern France (9 millions inhabitants) and collects all incident CD cases and data from CD multiplex families (families with 3 or more CD affected patients) in the Nord the Pas de Calais the Somme and the Seine Maritime. If the investigators could demonstrate that most CD cases from multiplex families were related to high frequency of NOD2 gene mutations, the investigators found some CD multiplex families without any NOD2 gene involvement. Thus in these families high prevalence of CD cases may rely on other major genetic susceptibility variant(s) that remain to be determined. this clinical research Whole Exome Sequencing protocol, aiming to highlight genetics mutations with major effect in CD has been initiated. This study is a familial genetic study with intra-familial controls. The genetics analyses are: Ascertain of no significant NOD2 mutation in the family members by Sanger DNA sequencing WES (CD patients and family controls unaffected subjects) Genotyping of all mutations found, case control and segregation analyses to validate their implication in CD.

Official Title
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Search for New Genetic Mutations Major Effect in Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Genetic: genetic analysis
* Biological: blood and stools samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Crohn disease subject EPIMAD family with, at least, 3 Crohn disease subjects Exclusion Criteria: Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Crohn disease subject<br>Crohn disease affected subject | Genetic: genetic analysis<br>* genetic (Whole Exome Sequencing )<br>Biological: blood and stools samples<br>* biological collection<br>|
| family control subject<br>family control unaffected subject | Genetic: genetic analysis<br>* genetic (Whole Exome Sequencing )<br>Biological: blood and stools samples<br>* biological collection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NOD2 gene status | One of the main inclusion criteria is the absence in the family (and thus in the proband) of any NOD2 mutation that could be related with the high occurrence of Crohn's Disease in the family. So verification of the lack of CD related NOD2 gene mutation is a prerequisite to the inclusion of the family in the protocol. This is achieved by Sanger sequencing of all exons, exon-intron junctions and search for already described intronic mutations in the family proband. | 8 months after recruiting | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole Exome Sequencing | Whole Exome Sequencing will be performed in every subject from all families. All genetic variants will be filtered with bioinformatic tools. Genetic variants with putative biological effect, presents in affected CD patients and absents in their unaffected relatives will be further investigated (i.e. cosegregation with the disease, involvement in a given pathway....). This study remains a pilot study to identify genetic variants that may be involved in Crohn's Disease. | 10 months after recruiting | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genetic