GENE LOCALIZATION FOR AN AUTOSOMAL-DOMINANT FAMILIAL PERIODIC FEVER TO 12P13

We report gene localization in a family with a benign autosomal domina nt familial periodic fever (FPF) syndrome characterized by recurrent f ever associated with abdominal pain. The clinical features are similar to the disorder previously described as familial Hibernian fever, and they differ from familial Mediterranean fever (FMF) in that FPF episo des usually do not respond to colchicine and FPF is not associated wit h amyloidosis. Frequent recombination with the marker D16S2622, <1 Mb from FMF, at 16p13.3, excluded allelism between these clinically simil ar conditions. Subsequently, a semiautomated genome search detected li nkage of FMF to a cluster of markers at 12p13, with a multipoint LOD s core of 6.14 at D12S356. If penetrance of 90% is assumed, the FPF gene maps to a 19-cM interval between D12S314 and D12S364; however, if com plete penetrance is assumed, then FPF maps to a 9-cM region between D1 2S314 and D12S1695. This interval includes the dentatorubropallidoluys ian atrophy locus, which, with FPF, gave a maximum two-point LOD score of 3.7 at a recombination fraction of 0. This is the first of the per iodic-fever genes, other than FMF, to be mapped. Positional candidate genes may now be selected for mutation analysis to determine the molec ular basis for FPF. Together with the recent identification of the def ective gene in FMF, identification of a gene for FPF might provide new insights into the regulation of inflammatory responses.