Búsqueda de mutaciones en el gen del receptor beta de hormonas tiroideas en familias argentinas no relacionadas con resistencia a hormonas tiroideas.

C. RIVOLTA,; C. OLCESE,; A. CHIESA,; L. GRUÑEIRO-PAPENDIECK,; S. IORCANSKY,; V. HERZOVICH,; S. MALLEA GIL,; C. FC. FEIJOO,; A. GAUNA,; C. BALLARINO,; M STIVEL; H. TARGOVNIK

Mar del Plata – Argentina,

Congreso; XIX Reunión de la Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP),; 2007

SLEP

Resistance to thyroid hormone (RTH) syndrome is a genetic disorder with a dominant mode of transmission characterized by a variable clinical state and increased thyroid hormone levels with an inappropriately normal or elevated level of TSH. RTH is linked to the thyroid hormone receptor beta (TRbeta) gene. 11 unrelated argentinian families with clinical evidences of RTH were studied. In order to identify mutations causing this pathology, genomic DNA was isolated from blood cells and the exons 9 and 10 of the TRbeta gene (corresponding to the ligand-binding domain), including the flanking intronic regions were amplified by PCR. DNA sequences from each amplified fragment were performed with the Taq polymerase-based chain terminator method and using the specific TRbeta forward and reverse primers. Direct sequence analysis revealed 3 novel missense mutations in exon 9. The first, a c.991A>G transition that results in a p.N331D substitution. The second, a c.1022T>C transition results in a  p.L341P. The third, c.1036C>T transition causing a p.L346F change. 4 novel mutations were identified in exon 10: c.1293A>G; p.I431M, c.1339C>A; p.P447T, c.1358C>T; p.P453L and c.1297-1304delGCCTGCCA; p.A433fsX461. In addition, 2 previously reported missense mutations have been identified, one of them in exon 9: c.1012C>T; p.R338W and the other in exon 10:  c.1357C>A; p.P453T (detected in three patients). The molecular diagnosis of RTH is important to determinate the appropriate treatment in those symptomatic patients to ameliorate features of hyper or hypothyroidism.