Clinical, Biochemical and Molecular Findings in Patients with Congenital Hypothyroidism Due to Mutations in the Thyroid Peroxidase (TPO) Gene.

TESTA, GRACIELA; BELFORTE, FIORELA SABINA; SOBRERO, GABRIELA; OLCESE, MARÍA CECILIA; RIVOLTA, CARINA MARCELA; TARGOVNIK, HÉCTOR MANUEL; MIRAS, MIRTA

Cartagena de Indias

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

Sociedad Latino-Americana de Endocrinología Pediátrica (SLEP)

13 Introduction and Objectives: Mutations in TPO gene are the most common cause for dyshormonogenesis. Its produce a variable with autosomal recessive inheritance. Objective: To describe the clinical, biochemical and molecular findings in a cohort of patients with congenital hypothyroidism, goiter, and high thyroglobulin levels. Methods: We studied 11 patients from 7 unrelated families, 6 of them diagnosed by newborn screening. Ultrasound and Tc99-scintigraphy were performed and TSH, T4, Free T4, T3 and TG were measured (EQLIA). The promoter and the 17 exons of the TPO were amplified by PCR, along with its flanking intronic regions. The products were analyzed with SSCP and those with differential migration were sequenced. Results: Goiter characteristics, as well as T4, Free T4, T3 and TSH levels, were similar. Three new mutations were identified: p.R595K (exon11); p.V748M (exon13), and g.IVS16-2A>C (intron16). Mutations in TPO gene were found in homozygosis in 2/11 patients, in composed heterozygosis in 6/11, and in 3/11 patients a single mutated allele was detected in exons 8, 13 and in intron16. Conclusion: Our findings confirm genetic heterogeneity of the defects in TPO gene. Identifications of new mutations can be useful to better understand physiopathology of congenital hypothyroidism.