Mapping a dominant form of multinodular goiter to chromosome Xp22

Multinodular goiter (MNG) is a common disorder characterized by a nodular e nlargement of the thyroid gland and occurring with a female:male ratio of 5 :1. This article reports the analysis of an Italian three-generation pedigr ee MNG, including 10 affected females and 2 affected males. After linkage t o candidate regions previously implicated in various forms of goiter was ex cluded, a novel MNG locus was searched. Because no male-to-male transmissio n was present in the study pedigree, an X-linked autosomal dominant pattern of inheritance was hypothesized. Therefore, 18 markers spaced at 10-cM int ervals on the ii chromosome were examined. A significant LOD score was obse rved in the Xp22 region, where marker DXS1226 generated a maximum LOD score of 4.73 at a recombination fraction of 0. Analysis of six flanking microsa tellites confirmed these data, and haplotype inspection delimited a 9.6-cM interval lying between DXS1052 and DXS8033.