title: A molecular analysis and long-term follow-up of two siblings with severe congenital hypothyroidism carrying the IVS30+1G>T intronic thyroglobulin mutation.
abstract: 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. METHOSD: 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 non-nodular 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.
authors.affiliation: University of São Paulo Medical School, SP, Brazil. ilearubi@usp.br
authors.forename: Ileana G S
authors.initials: IG
authors.lastname: Rubio
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Galrao
authors.forename: Viviane
authors.initials: V
authors.lastname: Pardo
authors.forename: Meyer
authors.initials: M
authors.lastname: Knobel
authors.forename: Roberta F
authors.initials: RF
authors.lastname: Possato
authors.forename: Rosalinda R Y
authors.initials: RR
authors.lastname: Camargo
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Cristina T
authors.initials: CT
authors.lastname: Kanamura
authors.forename: Simone A
authors.initials: SA
authors.lastname: Gomes
authors.forename: Geraldo
authors.initials: G
authors.lastname: Medeiros-Neto
mesh_terms: D000293:Adolescent; D002648:Child; D003409:Congenital Hypothyroidism / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009154:Mutation; D035781:Siblings; D013954:Thyroglobulin / Q000235:genetics*; D016606:Thyroid Nodule / Q000235:genetics / Q000473:pathology
chemical_list: D013954:Thyroglobulin