Search for genetic variants in the retinoid X receptor-gamma-gene by polymerase chain reaction-single-strand conformation polymorphism in patients with resistance to thyroid hormone without mutations in thyroid hormone receptor beta gene.
Resistance to thyroid hormone (RTH) is an inherited disease characterized by reduced tissue sensitivity to thyroid hormone. Approximately 90% of subjects with RTH have mutation in the thyroid hormone receptor beta (TRbeta) gene. Approximately 10% of subjects diagnosed as having RTH do not carry mutation in the TRbeta gene. A possible linkage was reported with the retinoid X receptor-gamma (RXR-gamma) gene in two families. The aim of this study is to search for mutation within the RXR-gamma gene in unrelated subjects with diagnosed RTH without mutations in the TRbeta gene. Four subjects with RTH were studied, and sequence variants in the RXR-gamma gene were searched by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). Analysis of all the 10 exons of the RXR-gamma gene, including intron-exon boundaries, promoter region and 3' untranslated region (UTR) reveled two variant bands in subjects II and III. Sequencing of these variants showed two single nucleotide polymorphisms (SNPs): 447C > T in exon 3 for patients II and IVS9 + 6A > G for patient III. Both SNPs were also present at high frequency in a group of normal subjects and in nonaffected relatives of subject III. In conclusion, in patients with RTH we have found two SNPs in the RXR-gamma gene; these SNPS are common in the general population, thus excluding a role for the RXR-gamma gene in these patients.
Romeo
Stefano
S
Department of Clinical Sciences, Division of Endocrinology, University of Rome La Sapienza, Rome, Italy.
Menzaghi
Claudia
C
Bruno
Rocco
R
Sentinelli
Federica
F
Fallarino
Mara
M
Fioretti
Francesca
F
Filetti
Sebastiano
S
Balsamo
Armando
A
Di Mario
Umberto
U
Baroni
Marco G
MG
D000328:Adult; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006042:Goiter / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D047491:Retinoid X Receptor gamma / Q000235:genetics*; D037042:Thyroid Hormone Receptors beta; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics*; D013963:Thyroid Hormones / Q000494:pharmacology*; D013972:Thyrotropin / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D017931:DNA Primers; D011988:Receptors, Thyroid Hormone; D047491:Retinoid X Receptor gamma; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin