S. Ditudompo et al., A de novo L330S point mutation in thyroid hormone receptor beta gene in a thai female with resistance to thyroid hormone, ENDOCR J, 46(6), 1999, pp. 825-829
In the present study, we report a Thai female with a de novo mutation in th
yroid hormone receptor-beta (TR beta) gene causing resistance to thyroid ho
rmone (RTH). The patient was a 19 year-old woman who presented with goiter
for 1 year. Except for tachycardia she had no signs of thyrotoxicosis. Prev
iously she was treated with propylthiouracil based on the diagnosis of thyr
otoxicosis for 9 months and her goiter became more enlarged. The patient wa
s the only child of the family. Her parents were alive and healthy, and did
not have goiter or any other thyroid diseases. Physical examination reveal
ed no sign of thyrotoxicosis. Her thyroid gland was diffusely enlarged with
an estimated weight of 100 gm. Laboratory determinations revealed elevated
free T4, T3 and nonsuppressed TSH levels. Exon 9 of the TR beta gene was a
mplified by PCR and the DNA sequence was determined by dye terminator cycle
sequencing. Heterozygous point mutation in which T was replaced by C was d
etected at position 1274 (TTG to TCG) corresponding to a leucine to serine:
substitution at codon 330. No mutation was found in the parents indicating
that the mutation was de novo. :The nucleotide change created a restrictio
n site for Tag 1 restriction endonuclease and the mutation was confirmed by
restriction fragments length polymorphism. The same nucleotide change has
been reported in a family with RTH.