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.

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.

Inclusion Criteria:

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

Exclusion Criteria:

• Pregnant or lactating women

Crohn disease subject