AUSTRALIAN CROHN'S DISEASE: ANALYSIS OF THE IBD1 FRAMESHIFT MUTATION

Le résumé fourni par la source

The inflammatory bowel diseases are amongst the most common complex genetic diseases with a combined prevalence of ∼200 per 100 000. Approximately 10% of affected individuals have an affected family member; disease modelling suggests that there are a number of susceptibility genes interacting with environmental triggers. Genome scans from around the world have implicated > 5 separate genetic localisations; one, the IBD1 locus on chromosome 16, was confirmed in an international collaborative effort1. That study reported a combined multipoint LOD score of 5.79 across 613 families and showed that the locus was Crohn's disease‐specific. This validation preceded the recent isolation and characterisation of IBD1 – the first complex disease gene to be fully described at the molecular level2,3. A number of functional mutations have been described in European and American populations that occur at twice the frequency in affected individuals as in controls. In those populations, linkage evidence offered variable support for the localisation, with the MLS varying from 3.4 to 2.5. In the Australian population however, the MLS is 6.3, suggesting that this gene and its mutations are of greater importance for the expression of the phenotype in Australian patients4. Using > 200 Australian multiplex IBD families, > 100 sporadic cases, and 100 normal individuals, we demonstrate that the IBD1 frameshift mutation occurs in ∼30% of CD cases. This is in contrast to the much lower percentage (ca. 8–10%) reported in European and American populations2,3. We relate these data to age of onset, disease type and site data.

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