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Morbus Crohn - CARD15

Clinical Features

Crohn's Disease is characterised by chronic, recurrent inflammation of the intestine. In contrast to Colitis ulcerosa (Cu), where inflammation is continual and confined to the rectum and/or colon, Crohn's disease produces intermittent centres of inflammation which can be located throughout the entire intestine. With most patients, however, inflammation is concentrated in the terminal ileum and colon.

In approximately 10% of inflammatory intestinal diseases confined to the rectum and colon, a definitive differentiation between Crohn's disease and Colitis ulcerosa is not possible; these are designated as "intermediate colitis". Both Crohn's disease and Colitis ulcerosa are autoimmune illnesses. Furthermore, extraintestinal inflammation of the skin, eyes and joints has also been observed.

Genetic Information

Along with mutations in the CARD15 gene (also known as NOD2, chromosome 16q12), mutations in the genes ABCB1, IBD2, IBD23, IBD24, IBD25, DLG5 and SLC224A  have also been described for patients affected by Crohn's disease. CARD15 codes for a protein 1040 amino acids in length which serves as an intracellular receptor for bacterial products (primarily LPS) in monocytes and induces NFkB activation. Mutation in the CARD15 gene are associated first and foremost with the clinical manifestation of Crohn's disease in the small intestine. Recent data suggest that variations in the number of copies in the gene, which codes for ß-defensin 2, is associated with Crohn's disease of the large intestine.

The CARD15 gene consists of 12 exons; the mRNA has a length of 4485 bp and codes a protein of 1040 amino acids. The following mutations represent approx. 81% of pathogenic CARD15 mutations: p.Arg702Trp (approx. 32%), p.Gly908Arg (approx. 18%), and p.Leu1007fsinsC (approx. 31%).

Prevalence

The incidence of Crohn's Disease is approx. 2 to 3 in every 100 000 people; the prevalence is approx. 250 to 500 in 100 000.

Diagnostic