Search Results
Search for other papers by Irene Campi in
Google Scholar
PubMed
Search for other papers by Maura Agostini in
Google Scholar
PubMed
Search for other papers by Federica Marelli in
Google Scholar
PubMed
Search for other papers by Tiziana de Filippis in
Google Scholar
PubMed
Search for other papers by Beatriz Romartinez-Alonso in
Google Scholar
PubMed
Search for other papers by Odelia Rajanayagam in
Google Scholar
PubMed
Search for other papers by Giuditta Rurale in
Google Scholar
PubMed
Search for other papers by Ilaria Gentile in
Google Scholar
PubMed
Search for other papers by Federica Spagnolo in
Google Scholar
PubMed
Search for other papers by Massimiliano Andreasi in
Google Scholar
PubMed
Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy
Search for other papers by Francesco Ferraù in
Google Scholar
PubMed
Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy
Search for other papers by Salvatore Cannavò in
Google Scholar
PubMed
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Laura Fugazzola in
Google Scholar
PubMed
Search for other papers by Krishna V. Chatterjee in
Google Scholar
PubMed
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Search for other papers by Luca Persani in
Google Scholar
PubMed
Introduction: Resistance to thyroid hormone β (RTHβ) is an inherited syndrome caused by dominant negative variants in the THRB gene (NM_000461.5). The clinical picture of RTHβ is variable, and patients harboring the same variant may display different degrees of disease severity. Case Presentation: A 30-year-old man presented with thyrotoxicosis and central hyperthyroidism and was found to have a novel variant in the exon 10 of THRB gene (c.C1282G, p.L428V), located within the third hot spot region of the C-terminal of the receptor. Surprisingly, the same variant was found in two other relatives with an apparent normal thyroid function at initial screening. After exclusion of a TSH-secreting adenoma and serum interference in the proband, and the finding that exogenous levothyroxine failed to suppress the TSH in the brother affected by nodular goiter, relatives’ thyroid function tests (TFTs) were reassessed with additional analytical method revealing biochemical features consistent with RTHβ in all carriers of the p.L428V variant. Functional studies showed a slightly impaired in vitro transcriptional activity of p.L428V. Interestingly‚ the expression of the human p.L428V thyroid hormone receptor beta in the zebrafish embryo background generated a phenotype consistent with RTHβ. Conclusion: Variable results of TFTs on some immunoassays can be a cause of RTHβ diagnostic delay, but the genotype-phenotype correlation in this family and functional studies support p.L428V as a novel THRB variant expanding the spectrum of gene variants causing RTHβ. In vivo, rather than in vitro, functional assays may be required to demonstrate the dominant negative action of THRB variants.
