title: [Clinical and molecular study of five families with resistance to thyroid hormones].
abstract: OBJECTIVE
  Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype.
  
  
  METHODS
  THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures.
  
  
  RESULTS
  THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls.
  
  
  CONCLUSIONS
  Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TRβ independent.
authors.affiliation: UETeM, Departamento de Medicina, Facultad de Medicina, Universidad de Santiago de Compostela, Santiago de Compostela, La Coruña, España. joaquin.lado@ttuhsc.edu
authors.forename: Joaquin
authors.initials: J
authors.lastname: Lado Abeal
authors.forename: Ramón
authors.initials: R
authors.lastname: Albero Gamboa
authors.forename: David
authors.initials: D
authors.lastname: Araujo Vilar
authors.forename: Olga
authors.initials: O
authors.lastname: Barca Mallo
authors.forename: Ignacio
authors.initials: I
authors.lastname: Bernabeú Moron
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Calvo
authors.forename: Isabel
authors.initials: I
authors.lastname: Castro Piedras
authors.forename: Jesús
authors.initials: J
authors.lastname: Martin Calamata
authors.forename: Fernando
authors.initials: F
authors.lastname: Palos Paz
authors.forename: Roberto
authors.initials: R
authors.lastname: Peinó
authors.forename: Diego
authors.initials: D
authors.lastname: Peteiro
authors.forename: Berta
authors.initials: B
authors.lastname: Victoria
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002648:Child; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005799:Genes, Dominant; D006042:Goiter / Q000097:blood / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D017354:Point Mutation; D037042:Thyroid Hormone Receptors beta / Q000235:genetics* / Q000502:physiology; D018382:Thyroid Hormone Resistance Syndrome / Q000097:blood / Q000235:genetics*; D013963:Thyroid Hormones / Q000097:blood
chemical_list: C489676:KLF9 protein, human; D051741:Kruppel-Like Transcription Factors; D009124:Muscle Proteins; C100360:RCAN2 protein, human; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones