Molecular findings in patients with congenital hypothyroidism due to mutations in the thyroglobulin gene.

SOBRERO, G.; MACHIAVELLI, GLORÍA ANGÉLICA; CITTERIO, CINTIA ELIANA; MUÑOZ, L.; RIVOLTA, CARINA MARCELA; SILVANO, L.; TESTA, G.; MARTÍN, S. ; TARGOVNIK , HÉCTOR MANUEL; MIRAS, M.

Cartagena de Indias

Congreso; XXII Annual Meeting of the Sociedad Latino-Americana de Endocrinología Pediátrica (SLEP); 2011

Sociedad Latino-Americana de Endocrinología Pediátrica (SLEP)

Resumen 12 Introduction and Objectives: Thyroglobulin (TG) is a 660 kDa-glycoprotein coded by a single copy gene 270 kb long that maps on chromosome 8q24.2–8q24.3. TG gene mutations are associated with congenital goiter and hypothyroidism with considerable phenotype variation. To identify mutations in the TG gene in patients with goiter, hypotiroidism and low serum TG levels. Methods: We studied nine patients from five nonconsanguineous families. The promoter and the coding regions of the TG gene, with the flanking intronic regions, were analysed by direct DNA sequencing. Results: Three novel TG mutations were identified: p.Y107X(exon4), p.C1262Y(exon17), and p.K1803fsX1833(exon28) and three previously reported mutations: p.R277X(exon7), p.A2215D(exon38) and p.R2317X(exon40). Two patients carried a compound heterozygous for p.K1803fsX1833/p.R2317X and p.Y107X/p.C1262Y mutations; five patients from two unrelated families showed a homozygous p.R277X substitution. The remaining, two patients with typical phenotype, had a single p.A2215D mutated allele. Conclusion: We report the occurrence of three new mutations of the TG gene. The prevalence of a limited number of mutations in each population will facilitate molecular genetic testing. The continued study of TG mutations may be helpful to understand the pathophysiology of hereditary diseases, carrier identification and genetic counseling.