Objective: To investigate genetic susceptibility in the first Indian family identified as having an autosomal dominantly inherited periodic fever syndrome. The inflammatory disease was characterized chiefly by arthralgia, skin rashes, and AA amyloidosis.
Methods: Markers from known periodic fever susceptibility loci were investigated in 7 affected and 11 healthy members of a north Indian family. These included the TNFRSF1A locus (formerly known as TNFRI), which is involved in autosomal dominant tumor necrosis factor receptor-associated periodic syndrome on chromosome 12p13, the familial Mediterranean fever locus (MEFV) on chromosome 16p13, the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) locus on chromosome 12q24, and the Muckle-Wells syndrome/familial cold urticaria (MWS/FCU) locus on distal chromosome 1q44.
Results: Linkage to both TNFRSF1A and MEFV was definitively excluded, and DNA sequencing of these genes revealed no mutations. Furthermore, there was no evidence of linkage to the HIDS locus. In contrast, significant logarithm of odds scores for 5 markers from the MWS/FCU region were obtained in this family, and the disease segregated with the same haplotype in all affected members.
Conclusion: We have identified an inherited inflammatory disease in a north Indian family with clinical features overlapping some of those of MWS and FCU. The susceptibility gene maps to distal chromosome 1q44, a region already implicated in both MWS and FCU. Different mutations in the same (or a closely related) gene may be responsible for an inflammatory disease with a broad phenotype among diverse ethnic populations.