RESISTANCE TO THYROID-HORMONE IN A FAMILY CAUSED BY A NEW POINT MUTATION L330S IN THE THYROID RECEPTOR (TR) BETA-GENE

Resistance to thyroid hormone (RTH) is an inherited defect manifesting as variable tissue hyporesponsiveness to thyroid hormone, usually cau sed by mutations in the thyroid hormone receptor beta (TR beta) gene. Up to now 78 mutations in this gene have been identified, mostly clust ered in two regions located in exon 9 and 10. We describe a new point mutation replacing the normal thymidine-1274 with a cytosine that resu lts in the substitution of the normal leucine-330 with a serine (L330S ) in the receptor protein. This mutation was identified in an 11-year- old boy who presented with symptoms and signs suggestive of both hyper thyroidism and hypothyroidism. Interestingly a mutation in the same co don (L330F) has been previously described in a patient who presented w ith stigmata suggestive of thyrotoxicosis.