C105fs114x Thyrotropin Beta-Subunit Gene Mutation Resulting in Congenital Central Hypothyroidism: A Genetic Study of a Brazilian Family

A. SANTOS; B. LARA; H. PALHARES; B. PIRES FERREIRA; H. DOMENE; P. SCAGLIA; G. SOUSA; M.F. BORGES

Cartagena de Indias

Congreso; XXII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2011

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

C105fs114x Thyrotropin Beta-Subunit Gene Mutation Resulting in Congenital Central Hypothyroidism: A Genetic Study of a Brazilian Family A. Santos1, B. Lara1, H. Palhares1, B. Pires Ferreira1, H. Domené2, P. Scaglia2, G. Sousa2, M.F. Borges2 ¹Universidade Federal do Triângulo Mineiro, Minas Gerais, Uberaba, Brasil; ²Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Hospital de Niños R. Gutiérrez-Centro de Investigaciones Endocrinológicas (CEDIE), División de Endocrinología, Buenos Aires, Argentina Introduction and Objectives: Central congenital hypothyroidism (CCH) is a rare disease that can result from mutations on genes that regulate pituitary development. We report molecular analysis of a boy with C105fs114X TSH beta subunit gene mutation and his family. Methods: Revision of medical records. Results: A child presented CCH classical symptoms at 5 months old, not revealed by neonatal  screening. Born from consanguineous parents, cesarean delivery, post-term, 4080g weigh and 53cm length. TSH:1.6μUI/mL (0.38?4.5); FT4: 0.1ng/dL (0.8?2.3); TPOAb < 10UI/L; TgAb: < 20UI/L;Glucose: 55mg/dL; Cortisol: 12.1μg/dL; Prolactin: 22.4ng/mL; H: 15.9ng/mL. Genotyping for beta TSH gene mutation was performed by PCR followed by restriction enzyme analysis with SnaBI, as the single base deletion (822delT) at codon 105 of the beta-TSH gene introduces a new SnaBI restriction site in exon 3, disclosing the C105fs114X mutation. The boy was homozygous; parents and sister heterozygous. Conclusions: The C105fs144X mutation, described by Medeiros-Neto et al.(1996) in two Brazilian families with CCH, was afterwards found in Europe, USA and Argentina in non-consanguineous families, differently from this case (parents are first degree cousis). It results in a truncated beta TSH subunit and seems to be the most prevalent mutation in the general population.