TARGOVNIK Hector Manuel
congresos y reuniones científicas
FlVE NEW CASES OF CONGENITAL GOITROUS HYPOTHYROIDISM DUE TO A p.R277X MUTATION IN THE THYROGLOBULIN GENE: THIS MUTATION IS THE RESULT OF A MUTATIONAL HOT SPOT
PARDO, VIVIANE; RUBIO, ILEANA GS; KNOBEL, MEYER; CHAGAS, ANTONIO; DIAS, VERA; VIANA, MARIA; TONIOLO, JUSSARA; RIVOLTA, CARINA; MOYA, CHRISTIAN; TARGOVNIK, HÉCTOR; MEDEIROS-NETO, GERALDO
Buenos Aires, Argentina
Congreso; 13th International Thyroid Congress; 2005
Sociedad Latinoamericana de Tiroides
Congenital hypothyroidism is one of the most common hereditary endocrine disorders, which affects 1:4000 newborns, frequently but not always diagnosed by neonatal screening. Mutations in the thyroglobulin (TG) gene have been reported to be one of the defects in thyroid biosynthesis causing congenital hypothyroidism (CH) in a 7% of frequency. In this study we looked for mutations in the TG gene in eleven patients from nine not related families. The deficiency of the TG synthesis was confirmed in all the patients by the measurement of serum TG 24 and 48 h after the stimulation by an injection of recombinant human TSH (0.45mg). In all patients serum TG values remained low ( < 0.5 - 1.9ng/ml). The methods used in this study were: DNA extraction from peripheral blood leukocytes, PCR to amplify the 48 exons of TG gene using intronic primers, insertion/deletion polymorphism, microsatellites and exonic single-nucleotide polymorpbism (SNP) genotyping. In five patients we were able to identify the previously described mutation c.886 C > T in exon 7 (p.R277X) that create a premature stop codon. In three patients this mutations was in homozigous form while in two patients it was in heterozygous form. The analysis of SNPs of the TG gene from the patients with the p.R277X suggests that this mutation is an independently recurrent mutation. CONCLUSION: These results suggest that the p.R277X mutation is among the more cornmon TG gene mutations. Haplotype studies indicate that a mutational hot spot could explain the recurrence of this mutation.