Genetic analyses and evaluation of peripheral parameters of thyroid hormone action for the differential diagnosis of RTH. A novel heterozygous missense mutation (M334T) discovered

D. Mannavola, G. Vannucchi, L. Fugazzola, N. Cerutti, L. Persani, Paolo Beck-Peccoz

Research output: Contribution to journalArticle

Abstract

Resistance to thyroid hormone (RTH) is a rare disease characterized by goiter and elevated free thyroid hormone (TH) levels in the presence of detectable concentrations of TSH. Most RTH patients harbor mutations in the ligand binding domain (LBD) of thyroid hormone receptor β (TRβ) gene, without a clear correlation between genotype and phenotype. Clinical, biochemical and genetic analyses were performed in several members of one family, because the index case presented with elevated free TH, measurable TSH and no hyperthyroid manifestations, but with a pituitary lesion at MRI. High free TH levels and TSH concentrations in the normal range were found also in 4 relatives. The presence of euthyroidism in all patients together with peripheral parameters of TH action in the normal range led to the diagnosis of generalized RTH (GRTH). In the five affected members, the genetic analysis revealed a novel heterozygous missense mutation at codon 334 (M334T). A different mutation at codon 334 was previously described in association with selective pituitary resistance to thyroid hormone (PRTH). Therefore, we confirm that substitutions at Methionine 334 are critical for the structural integrity of TRβ LBD. The association of different phenotypes with substitutions affecting the same codon is another contribution confirming that RTH phenotype does not generally depend upon the site of the mutation in the LBD of TRβ1.

Original languageEnglish
JournalJournal of Endocrinological Investigation
Volume25
Issue number2
Publication statusPublished - 2002

Keywords

  • ACE
  • Glycoprotein α-subunit (α-GSU)
  • ICTP
  • Mutation
  • Peripheral parameters
  • Pituitary incidentaloma
  • RTH
  • SHBG
  • Thyroid hormone resistance syndrome
  • TRβ gene

ASJC Scopus subject areas

  • Endocrinology

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