title: E449X mutation in the thyroid hormone receptor beta associated with autoimmune thyroid disease and severe neuropsychomotor involvement.
abstract: OBJECTIVE
  To report the clinical and molecular aspects of a patient with a diagnosis of Resistance to Thyroid Hormone (RTH) harboring the E449X mutation associated with autoimmune thyroid disease and severe neuropsychomotor retardation.
  
  
  METHODS
  We present a case report including clinical and laboratory findings, and molecular analysis of a Brazilian patient with RTH.
  
  
  RESULTS
  A 23-year old male presented hyperactivity disorder, attention deficit, delayed neuropsychomotor development, and goiter. Since the age of 1 year and 8 months, his mother had sought medical care for her son for the investigation of delayed neuropsychomotor development associated with irritability, aggressiveness, recurrent headache, profuse sudoresis, intermittent diarrhea, polyphagia, goiter, and low weight. Laboratory tests revealed normal TSH, increased T3, T4, antithyroglobulin and antimicrosomal antibody titers. Increasing doses of levothyroxine were prescribed, reaching 200 microg/day, without significant changes in his clinical-laboratory picture. Increasing doses of tiratricol were introduced, with a clear clinical improvement of aggressiveness, hyperactivity, tremor of the extremities, and greater weight gain. Molecular study revealed a nonsense mutation in exon 10, in which a substitution of a guanine to tyrosine in nucleotide 1345 (codon 449) generates the stop codon TAA, confirming the diagnosis of RTH.
  
  
  CONCLUSIONS
  This patient has severe neuropsychomotor retardation not observed in a single previous report with the same mutation. This may reflect the lack of a genotype-phenotype correlation in affected cases with this syndrome, suggesting that genetic variability of factors other than beta receptor of thyroid hormone (TRbeta) might modulate the phenotype of RTH.
authors.affiliation: Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors.forename: Maria Helane Costa
authors.initials: MH
authors.lastname: Gurgel
authors.forename: Renan M
authors.initials: RM
authors.lastname: Montenegro Junior
authors.forename: Rejane Araujo
authors.initials: RA
authors.lastname: Magalhaes
authors.forename: Grayce Ellen da C Paiva
authors.initials: GE
authors.lastname: Lima
authors.forename: Renan Magalhães
authors.initials: RM
authors.lastname: Montenegro
authors.forename: Patricia Kunzle Ribeiro
authors.initials: PK
authors.lastname: Magalhães
authors.forename: Lea Maria Zanini
authors.initials: LM
authors.lastname: Maciel
mesh_terms: D001327:Autoimmune Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype; D011595:Psychomotor Agitation / Q000175:diagnosis* / Q000188:drug therapy; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D018382:Thyroid Hormone Resistance Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D013963:Thyroid Hormones / Q000378:metabolism; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones