An autosomal dominant periodic fever associated with AA amyloidosis in a north Indian family maps to distal chromosome 1q

Objective. To investigate genetic susceptibility in the first Indian family identified as having an autosomal dominantly inherited periodic fever synd rome. The inflammatory disease was characterized chiefly by arthralgia, ski n rashes, and AA amyloidosis. Methods. Markers from known periodic fever susceptibility loci were investi gated 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 synd rome 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 c old urticaria (MWS/FCU) locus on distal chromosome 1q44. Results. Linkage to both TNFRSF1A and MEFV was definitively excluded, and D NA sequencing of these genes revealed no mutations. Furthermore, there was no evidence of linkage to the HIDS locus. In contrast, significant logarith m of odds scores for 5 markers from the MWS/FCU region were obtained in thi s family, and the disease segregated with the same haplotype in all affecte d 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 1q34, a region alrea dy implicated in both MWS and FCU, Different mutations in the same (or a cl osely related) gene may be responsible for an inflammatory disease with a b road phenotype among diverse ethnic populations.