title: 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.
abstract: 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.
authors.affiliation: Department of Clinical Sciences, Division of Endocrinology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Romeo
authors.forename: Claudia
authors.initials: C
authors.lastname: Menzaghi
authors.forename: Rocco
authors.initials: R
authors.lastname: Bruno
authors.forename: Federica
authors.initials: F
authors.lastname: Sentinelli
authors.forename: Mara
authors.initials: M
authors.lastname: Fallarino
authors.forename: Francesca
authors.initials: F
authors.lastname: Fioretti
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.forename: Armando
authors.initials: A
authors.lastname: Balsamo
authors.forename: Umberto
authors.initials: U
authors.lastname: Di Mario
authors.forename: Marco G
authors.initials: MG
authors.lastname: Baroni
mesh_terms: 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
chemical_list: D017931:DNA Primers; D011988:Receptors, Thyroid Hormone; D047491:Retinoid X Receptor gamma; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin