Three novel point mutations at nucleotides 1249, 1282, and 1614 (exons 9 and 10) 
of the human thyroid hormone receptor-beta gene were observed in six individuals 
affected by the syndrome of resistance to thyroid hormone. All three mutations 
occurred in a heterozygous pattern and caused the following changes in the 
mature form of the receptor protein: Asp322 to Asn, Glu333 to Gln, and Lys443 to 
Asn, respectively. The first and third point mutations arose in two unrelated 
families from eastern Sicily, whereas the second concerned an individual from 
southern Calabria, apparently presenting a sporadic form of the resistance 
syndrome. The clinical and biochemical features of resistance to thyroid 
hormone, both before and after the administration of thyroid hormones, highlight 
the striking intrafamilial heterogeneity in the phenotypical presentation of the 
syndrome.