After one round of clone walking, the physical map covered more than 80% of the broad Blau syndrome interval.

The gene subsequently characterized as having mutations in Blau syndrome families was not in the interval.

The CES1 gene was, therefore, excluded as a candidate for the Blau syndrome.

We also excluded the four candidate genes as the genes harbouring mutations causing the Blau syndrome.

Mutations in NOD2 are associated with the Crohn's disease or Blau syndrome.

Mutations in this gene have been associated with Crohn's disease and Blau syndrome and graft-versus-host disease.

MMP2 was placed outside of a refined Blau syndrome interval that excluded several cM centromeric from D16S408.

Additional files 1 Physical map of the Blau syndrome interval showing BAC clone contigs and markers.

These 41 non-redundant CITB clones in the contigs covered less than 50% of the broad Blau syndrome interval.

Restated, Blau syndrome is a rare autosomal dominant disorder characterized by granulomatous polyarthritis, panuveitis, cranial neuropathies, and exanthema.

Seven thirteen-marker haplotypes could be assigned unambiguously (Table 3) using extended pedigree structures (data not shown), however, none of them was associated with the Blau syndrome phenotype.

The NOD2 gene is linked to inflammatory diseases such as inflammatory bowel disease/Crohn's Disease and Blau syndrome.

This contig map, however, does not cover the entire Blau syndrome region; it ends at the site of marker D16S2758 in our physical contig (see additional data file 1).

We were hampered in our efforts to fine map the gene for the Blau syndrome because we were faced with an uncertain marker order in maps that had many inconsistencies.

MMP15 and SCYA17 were located telomeric to D16S408 and thus outside the Blau syndrome interval and were excluded from further studies.

Blau syndrome is characterized by familial granulomatous arthritis, uveitis, and skin granulomas, comprising an autosomal dominantly inherited syndrome that overlaps both sarcoidosis and granuloma annulare.

The phenotype of the Blau syndrome resembles another multisystem granulomatous disorder, Crohn's disease (MIM 266600), and another autoimmune disease, psoriasis (MIM 177900).

While our studies were in progress, other groups detected mutations in the CARD15 gene for a subset of Crohn's disease patients, and in three small Blau syndrome families [ 11 12 ] .

In our G3 RH map CES1 was located outside a subsequently refined Blau syndrome interval that excluded several cM centromeric to D16S408, thus confirming the lack of association between CES1 haplotypes and the disease phenotype.