Three Japanese patients from two families with generalized resistance to thyroid hormone with mutations in exon 9 of the thyroid hormone receptor beta gene.

Resistance to thyroid hormone (RTH) is a genetic disorder caused by mutations in the thyroid hormone receptor (TR) beta gene. The mutations are clustered in two regions: exon 9 and exon 10. To date, only one patient with an exon 9 mutation has been reported in Japan. We herein report three patients from two Japanese families with RTH and mutations in exon 9. A 52-year-old woman and her 18-year-old daughter, both with inappropriate secretion of TSH (SITSH) were diagnosed simultaneously with generalized RTH. Molecular analysis revealed a G345D mutation. An 11-year-old girl with SITSH, whose only manifestation was a goiter, had an R338W mutation, which is frequently associated with pituitary RTH. Thus, RTH with mutations in exon 9 of the TR beta gene is not so rare in Japan.