Thyroid Hormone Receptor β (THRB) defect
s, typically tran
smitted a
s auto
somal dominant trait
s, cau
se Re
si
stance to Thyroid Hormone (RTH). We analyzed the THRB gene in thirteen South American patient
s with clinical evidence RTH from eleven unrelated familie
s. Sequence analy
si
s revealed
seven novel mi
ssen
se mutation
s. Four novel mutation
s were identified in exon 9. The fir
st, a c.991A>G tran
sition which originate
s a
sub
stitution of a
sparagine by a
spartic acid (p.N331D). The
second nucleotide alteration con
si
st
s of a guanine to cyto
sine tran
sver
sion at po
sition 1003 (c.1003G>C) and re
sult
s in
sub
stitution of the alanine at codon 335 by proline (p.A335P). The third mutation, a c.1022T>C tran
sition produce
s a change of leucine by proline (p.L341P). The fourth mutation detected in exon 9 wa
s a c.1036C>T tran
sition which replace
s the leucine at codon 346 by phenylalanine (p.L346F). The
sequencing of the exon 10 detected three novel mi
ssen
se mutation
s. The fir
st, a c.1293A>G tran
sition changing i
soleucine 431 for methionine (p.I431M). The
second, the cyto
sine at po
sition 1339 wa
s replaced by adenine (c.1339C>A) re
sulting in the replacement of proline by threonine (p.P447T). The third mutation detected in exon 10 wa
s a c.1358C>T tran
sition re
sulting in the
sub
stitution of proline at codon 453 by leucine (p.P453L). Finally,
sequencing analy
si
s of the THRB gene revealed three
sub
stitution
s previou
sly de
scribed (p.A268G, p.P453T and p.F459C). The p.P453T wa
s found in two patient
s.
In conclusion, we report thirteen patients with RTH caused by heterozygous mutations of the THRB gene. Seven of the identified mutations correspond to novel substitutions.