TARGOVNIK Hector Manuel
congresos y reuniones científicas
CONGENITAL HYPOTHYROID GOITER WITH DEFICIENT THYROGLOBULIN (TG) SYNTIIESIS: PRELIMINARY MOLECULAR APPROACH
CHIESA, ANA; RIVOLTA, CARINA MARCELA; CAPUTO, MARIELA; TARGOVNIK, HÉCTOR MANUEL; GRUÑEIRO PAPENDIECK, LAURA
Viña del Mar
Congreso; XVIII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2006
Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)
Introduction and Aim: Congenital hypothyroidism (CH), the most common hereditary endocrine disorder, may be due lo defects in thyroid development (75%) and dyshonnonogenesis (25%). Among the latter, defects of TPO, DUOX2 and pendrin cause iodine organification defects and mutations of TG gene cause defective TG. We report the evaluation of patients with CH, goiter and TG synthesis defect. Patient and Methods: We studied 11/50 CH with goiter detected mostly by newbom screening, selected if they had at diagnosis or re-evaluation high TSH levels, low T4 and TG values. Eight underwent a perchlorate discharge test that was always negative (<10%). 22 of 48 exons of the TG gene were studied by DNA sequencing. Results: We found mutations in 7/11 patients. 1) Two hypothyroid siblings from non-consanguineous parents were compound heterozygotes for 886C®T in exon 7 and 4588C®T in exon 22, substitutions that resulted in a premature stop codon at arnino acids 277 (R277X) and 1511 (R1511X), respectively. 2) One patient was homozygous R277X mutation in exon 7. 3) Three patients were heterozygous R277X in exon 7.4) One patient had a heterozygous insertion in exon 7. Conclusion: Low TG levels in a goitrous hypothyroid patient suggest a TG synthesis defect. Seven of 11 patients with these features showed mutations in exon 7, two as compound heterozygotes, one homozygous, and four heterozygous with only one mutation found. Coinciding with previous reports, the R277X mulation was the most frequently found and could be considcred as a ´hot spot´. Consequently, il would be helpful consider investigation for this mutation in patients with defective TG synthesis.