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.