FAMILIAL NONTOXIC MULTINODULAR THYROID GOITER LOCUS MAPS TO CHROMOSOME-149 BUT DOES NOT ACCOUNT FOR FAMILIAL NONMEDULLARY THYROID-CANCER

Thyroid goiter is a common condition that is often associated with iod ine deficiency. Familial forms of goiter in areas not known to feature iodine deficiency are much less common. We have performed a genomic s earch on a single large Canadian family with 18 cases of nontoxic mult inodular goiter in which 2 individuals also had papillary lesions high ly suggestive of papillary carcinoma. A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at th e same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary). The gene encoding thyroid-stimulating hormone receptor (TS HR), which is located on chromosome 14q, is outside the linked region. To determine the role of this gene in familial nonmedullary thyroid c ancer (NMTC), we studied 37 smaller pedigrees each containing at least two cases of NMTC. Analysis by both parametric and nonparametric meth ods indicates that only a very small proportion of familial NMTC (poin t estimate 0.001, support intervals 0 - .6 under a dominant model) is attributable to MNG1.