Search for New Genetic Mutations Major Effect in Crohn's Disease (MC-WES)

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.

Study Overview

• Status: Completed
• Conditions: Crohn Disease
• Intervention / Treatment: Genetic: genetic analysis; Biological: blood and stools samples

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• France
  • Lille, France
    • CHRU, Hôpital Claude Huriez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Crohn disease subject

Description

Inclusion Criteria:

• Crohn disease subject
• EPIMAD family with, at least, 3 Crohn disease subjects

Exclusion Criteria:

• Pregnant or lactating women

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Crohn disease subject; Crohn disease affected subject	Genetic: genetic analysis; genetic (Whole Exome Sequencing ); Biological: blood and stools samples; biological collection
family control subject; family control unaffected subject	Genetic: genetic analysis; genetic (Whole Exome Sequencing ); Biological: blood and stools samples; biological collection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Corinne Gower, MD, PhD, University Hospital, Lille

Publications and helpful links

General Publications

• Frade-Proud'Hon-Clerc S, Smol T, Frenois F, Sand O, Vaillant E, Dhennin V, Bonnefond A, Froguel P, Fumery M, Guillon-Dellac N, Gower-Rousseau C, Vasseur F. A Novel Rare Missense Variation of the NOD2 Gene: Evidencesof Implication in Crohn's Disease. Int J Mol Sci. 2019 Feb 15;20(4):835. doi: 10.3390/ijms20040835.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: June 7, 2016
• First Submitted That Met QC Criteria: July 27, 2016
• First Posted (Estimate): August 1, 2016

Study Record Updates

• Last Update Posted (Actual): February 28, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: genetic
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 2013_53; 2014-A00023-44 (Other Identifier: ID-RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED