Monoallelic deletion in the 5 ' region of the thyroglobulin gene as a cause of sporadic nonendemic simple goiter

The cause of sporadic simple goiter is unknown in most cases. Family studie s have suggested that this disorder may have a genetic component in some pa tients. We have previously demonstrated that some cases of endemic and none ndemic simple goiter are associated with a mutation within exon 10 of the t hyroglobulin gene. Here we report a study of 50 cases diagnosed as having n onendemic simple goiter, and found 1 case with a large heterozygous deletio n within the thyroglobulin gene. The deletion involves the promoter region and the 11 first exons of this gene and is associated with a euthyroid stat e. We hypothesize that the absence of thyroglobulin synthesis from the dele ted allele may be responsible for a decreased level of thyroglobulin mRNA. Euthyroidism would be achieved by thyrotropin (TSH) stimulation but at the expense of goiter development.