Frontiers in Endocrinology (Jul 2024)

Clinical and molecular study of patients with thyroid dyshormogenesis and variants in the thyroglobulin gene

  • Mónica Fernández-Cancio,
  • Mónica Fernández-Cancio,
  • María Antolín,
  • María Antolín,
  • María Clemente,
  • María Clemente,
  • María Clemente,
  • María Clemente,
  • Ariadna Campos-Martorell,
  • Ariadna Campos-Martorell,
  • Ariadna Campos-Martorell,
  • Eduard Mogas,
  • Eduard Mogas,
  • Eduard Mogas,
  • Noelia Baz-Redón,
  • Noelia Baz-Redón,
  • Jordi Leno-Colorado,
  • Jordi Leno-Colorado,
  • Gemma Comas-Armangué,
  • Elena García-Arumí,
  • Elena García-Arumí,
  • Elena García-Arumí,
  • Laura Soler-Colomer,
  • Núria González-Llorens,
  • Núria Camats-Tarruella,
  • Núria Camats-Tarruella,
  • Diego Yeste,
  • Diego Yeste,
  • Diego Yeste,
  • Diego Yeste

DOI
https://doi.org/10.3389/fendo.2024.1367808
Journal volume & issue
Vol. 15

Abstract

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IntroductionDefects in any thyroid hormone synthesis steps cause thyroid dyshormonogenesis (THD). THD due to thyroglobulin (TG) gene variants is a cause of congenital hypothyroidism (CH) with a wide clinical spectrum, ranging from mild to severe permanent hypothyroidism. We present high-throughput sequencing results of patients with TG variants.MethodsA CH high-throughput sequencing-panel of the main genes involved in the regulation of thyroid hormonogenesis was performed to identify those TG variants that may be related to patient THD phenotype.ResultsWe identified 21 TG gene variants in 19 patients (11.8%) which could explain their phenotype. Ten of those (47.6%) were not previously described. CH was biochemically severe in these 19 patients. Eight of them were reevaluated after one month of discontinuing LT4 treatment and all had severe permanent hypothyroidism. We also identified another 16 patients who presented heterozygous TG variants, of whom, at reevaluation, five had mild permanent and only one had severe permanent hypothyroidisms.DiscussionsIn this study, 10 novel and 11 previously reported variants in the TG gene have been identified that could explain the phenotype of 19 patients from non-consanguineous families from a large THD cohort. Although not all these TG gene variants can explain all the patients’ THD phenotypes, some of them had severe or mild permanent hypothyroidism at reevaluation.

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