info:eu-repo/semantics/article
Genotyping of resistance to thyroid hormone in South American population. Identification of seven novel missense mutations in the human thyroid hormone receptor β gene
Fecha
2009-06Registro en:
Rivolta, Carina Marcela; Olcese, María Cecilia; Belforte, Fiorella Sabrina; Chiesa, Ana Elena; Gruñeiro Papendieck, Laura; et al.; Genotyping of resistance to thyroid hormone in South American population. Identification of seven novel missense mutations in the human thyroid hormone receptor β gene; Academic Press Ltd - Elsevier Science Ltd; Molecular And Cellular Probes; 23; 3-4; 6-2009; 148-153
0890-8508
CONICET Digital
CONICET
Autor
Rivolta, Carina Marcela
Olcese, María Cecilia
Belforte, Fiorella Sabrina
Chiesa, Ana Elena
Gruñeiro Papendieck, Laura
Iorcansky, Sonia
Herzovich, Viviana
Cassorla, Fernando
Gauna, Alicia Teresa
Gonzalez Sarmiento, Rogelio
Targovnik, Hector Manuel
Resumen
Thyroid Hormone Receptor β (THRB) defects, typically transmitted as autosomal dominant traits, cause Resistance to Thyroid Hormone (RTH). We analyzed the THRB gene in thirteen South American patients with clinical evidence RTH from eleven unrelated families. Sequence analysis revealed seven novel missense mutations. Four novel mutations were identified in exon 9. The first, a c.991A>G transition which originates a substitution of asparagine by aspartic acid (p.N331D). The second nucleotide alteration consists of a guanine to cytosine transversion at position 1003 (c.1003G>C) and results in substitution of the alanine at codon 335 by proline (p.A335P). The third mutation, a c.1022T>C transition produces a change of leucine by proline (p.L341P). The fourth mutation detected in exon 9 was a c.1036C>T transition which replaces the leucine at codon 346 by phenylalanine (p.L346F). The sequencing of the exon 10 detected three novel missense mutations. The first, a c.1293A>G transition changing isoleucine 431 for methionine (p.I431M). The second, the cytosine at position 1339 was replaced by adenine (c.1339C>A) resulting in the replacement of proline by threonine (p.P447T). The third mutation detected in exon 10 was a c.1358C>T transition resulting in the substitution of proline at codon 453 by leucine (p.P453L). Finally, sequencing analysis of the THRB gene revealed three substitutions previously described (p.A268G, p.P453T and p.F459C). The p.P453T was found in two patients. 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.