A Molecular Analysis and Long-Term Follow-up of Two Siblings with Severe Congenital Hypothyroidism Carrying the IVS30+1G > T Intronic Thyroglobulin Mutation

Autor(es)

Rubio, Ileana G. S. ^[1] ; Galrao, Ana Luiza ^[1] ; Pardo, Viviane ^[1] ; Knobel, Meyer ^[1] ; Possato, Roberta F. ^[1] ; Camargo, Rosalinda R. Y. ^[1] ; Ferreira, Marcelo A. ^[2] ; Kanamura, Cristina T. ^[3] ; Gomes, Simone A. ^[4] ; Medeiros-Neto, Geraldo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Thyroid Unit LIM 25, Div Endocrinol, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Div Pathol, BR-01246903 Sao Paulo - Brazil

^[3] Sao Paulo Publ Hlth Serv, Adolfo Lutz Inst, Sao Paulo - Brazil

^[4] Univ Fed Sergipe, Sch Med, Div Endocrinol, Aracaju, SE - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Arquivos Brasileiros de Endocrinologia e Metabologia; v. 52, n. 8, p. 1337-1344, NOV 2008.
• Citações Web of Science: 4

Resumo

Objective: To extend the molecular analysis of the IVS30+1G > T intronic thyroglobulin (TG) mutation, and to report the eleven year follow-up of the affected patients. Methods: Two siblings with severe congenital hypothyroidism with fetal and neonatal goiter, harboring the IVS30+1G > T mutation were included. Nodular and non-nodular thyroid tissue specimens were collected. Specific thyroid genes expression was evaluated by real-timePCR and by immunohistochemistry. Results: In non-nodular tissue specific thyroid genes mRNA were reduced when compared to normal thyroid sample. In the nodule, TPO and NIS expression was very low. Microscopic examinations showed very large follicular-lumina and swollen vesicles of endoplasmatic-reticulum. Strong cytoplasmatic and low follicular-lumen TG immunostaining were detected. Intracellular NIS, membrane TPO and TSHR immunostaining had higher positivity in nonnodular sample. Both patients had a long-term adequate developmental outcome, besides one patient have been lately-treated. Conclusions: IVS30+1G > T mutation not only lead to very enlarge endoplasmatic-reticulum, but also to alterations of specific thyroid genes expression. The clinical evolution of patients harboring these mutations strengthen the concept of the influence of environment, like iodine nutrition, to determine the final phenotypic appearance. (Arq Bras Endocrinol Metab 2008; 52/8:1337-1344) (AU)

• Processo FAPESP: 03/02989-8 - Hipotireoidismo congênito por deficiência na síntese de tireoglobulina: rastreamento e estudo funcional de mutações do gene da tireoglobulina
• Beneficiário: Viviane Lyrio Do Valle de Pardo Blois
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto