TARGOVNIK Hector Manuel
congresos y reuniones científicas
MUTATIONS IN THE THYROGLOBULIN GENE IN PATIENTS WITH CONGENITAL HYPOTHYROIDISM
PARDO, VIVIANE; RUBIO, ILEANA; KNOBEL, MEYER; CHAGAS, ANTONIO J.; DIAS, VERA M.A.; VIANA, MARIA F S.; TONIOLO, JUSSARA V.; TARGOVNIK, HECTOR; MEDEIROS-NETO, GERALDO
Vancouver, British Columbia, Canadá
Congreso; 76th Annual Meeting of the American Thyroid Association; 2004
American Thyroid Association
Congenital hypothyroidism is one of the most common hereditary endocrine disorders, which affects aproximately 1 in 4000 newborns, frequently but not always diagnosed by neonatal screening. Several mutations in the thyroglobulin (Tg) gene have been reported to be one of the defects in thyroid biosynthesis causing congenital hypothyroidism (CH). In this study we looked for mutations in the Tg gene in eight patients from six not related families from the same region of Brazil. The deficiency of the thyroglobulin synthesis was confirmed in all the patients by the measurement of serum Tg 24 and 48 h after the estimulation by an injection of recombinant human TSH (0.45mg). In all patients serum Tg values remained low (<0.5 1.9ng/ml). From the 48 exons of Tg gene 24 exons were analyzed sequenced. In four patients we were able to identify the previously described mutation 886 C>T in exon 7 (R277X). In three patients this mutations was in homozygous while in one patient it was in heterozygous form. We also identified the following polymorphisms: 3474 T>C in exon 16 (S1139S), 3753 A>G in exon 17 (E1232E), 3935 G>A in exon 18 (S1294D), and 5995 C>T in exon 33 (R1980W). A founder effect was suspected in this cohort and haplotype studies are being conducted to confirm this effect. In conclusion, mutation in the Tg gene would affect the structure of the translated protein and prevent its export to the colloid.