INVESTIGADORES
RIVOLTA Carina Marcela
congresos y reuniones científicas
Título:
CONGENITAL HYPOTHYROID GOITER WITH DEFICIENT THYROGLOBULIN (TG) SYNTHESIS: PRELIMINARY MOLECULAR APPROACH.
Autor/es:
CHIESA ANA; RIVOLTA CARINA M.; CAPUTO MARIELA; TARGOVNIK HÉCTOR M; GRUÑEIRO PAPENDIECK LAURA
Lugar:
Viña del Mar, República de Chile
Reunión:
Congreso; XVIII Ánnual Meeting of The Sociedad Latinoamericana de Endcrinología Pediátrica (SLEP); 2006
Institución organizadora:
Sociedad Latinoamericana de Endcrinología Pediátrica
Resumen:
Introduction and Aim: Congenital hypothyroidism (CH), the most common hereditary endocrine disorder, may be due to defects in thyroid development (75%) and dyshormonogenesis (25%). Among the latter, defects of TPO, DUOX2 and pendrin cause idodine organification defects and mutations of TG gene cause defective TG. We report the evaluation of patients with CH, goiter and TG synthesis defect. Patients and Methods: We studied 11/50 CH with goiter detected mostly by newborn 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 amino 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 heterogygous 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 heterozygous, one homozygous, and four heterozygous with only one mutation found. Coinciding with previous reports, the R277X mutation was the most frequently found and could be considered as a “hot spot”. Consequently, it would be helpful to consider investigation for this mutation in patients with defective TG synthesis.