Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44

The Muckle-Wells syndrome (MWS) is a hereditary inflammatory disorder chara cterized by acute febrile inflammatory episodes comprising abdominal pain, arthritis, and urticaria. Progressive nerve deafness develops subsequently, and, after several years, the disease is complicated by multiorgan AA-type amyloidosis (i.e., amyloidosis derived from the inflammatory serum amyloid -associated protein) (MIM 191900) with renal involvement and end-stage rena l failure. The mode of inheritance is autosomal dominant, but some sporadic cases have also been described. No specific laboratory findings have been reported. The genetic basis of MWS is unknown. Using a genomewide search st rategy in three families, we identified the locus responsible for MWS, at c hromosome 1q44. Our results indicate that the gene is located within a 13.9 -cM region between markers D1S2811 and D1S2882, with a maximum two-point LO D score of 4.66 (recombination fraction .00) at D1S2836 when full penetranc e is assumed. Further identification of the specific gene that is responsib le for MWS will therefore provide the first biological element for characte rizing MWS, other than doing so on the basis of its variable clinical expre ssion.