Thyroglobulin gene point mutation associated with non-endemic simple goitre.

Simple goitre is defined as an enlargement of the thyroid gland that is not the result of an inflammatory or neoplastic process and is not associated with thyrotoxicosis or myxoedema; the cause is unknown in most cases. Structural or regulatory defects in the proteins involved in thyroid metabolism might be involved in the functional abnormality that brings about the disorder. We have found a mutation within exon 10 of the thyroglobulin gene in 25 of 56 members of three families affected by simple goitre; 14 of the gene carriers had the disorder. DNA sequencing showed a mis-sense mutation within thyroglobulin gene exon 10, resulting in a glutamine to histidine substitution. Thus, some cases of non-endemic simple goitre are associated with a mutation at the thyroglobulin locus.