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TTF-2/FOXE1 gene polymorphisms in Sicilian patients with permanent primary congenital hypothyroidism

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Abstract

Thyroid transcription factor-2 (TTF-2/FOXE1) is a polyalanine domain protein that regulates thyroid embryogenesis, but very few patients with permanent primary congenital hypothyroidism (pCH) harbor germline mutations of this or other transcription factors that are involved in thyroid development that might explain the etiology of pCH. Variations within the polyalanine tract are found in a variety of genes and are often reported in association with malformation syndromes; pCH is frequently associated with thyroid malformations and extra-thyroidal malformations. Therefore, in this study we investigated whether alanine (Ala) length polymorphisms and non-polymorphic mutations of the TTF-2 gene in pCH patients might be involved in the pathogenesis of pCH. The entire coding region of the TTF-2 gene was analyzed in 57 Sicilian patients and 142 healthy controls. We found that the homozygous Ala14 polymorphism (Ala14/14) was less frequent in the pCH group than in the controls. In contrast, significantly more pCH patients than controls harbored the Ala16 polymorphism (Ala16/16 and Ala14/16). However, neither the Ala14/14 nor the Ala16 polymorphism was related to extra-thyroidal malformations. Two of the 57 patients carried Ala11/14 and Ala12/14, and one Ala14/14 patient also had the silent polymorphism 387 C/T (Leu129Leu). Other than known polymorphic variants we found no mutation in the TTF-2 gene. Therefore, this study demonstrates that mutations in the TTF-2 gene are rare in pCH patients and suggests that variations in the length of the Ala-tract could at least partially explain the etiology of pCH but not that of extra-thyroidal malformations.

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Authors and Affiliations

  1. Sezione di Endocrinologia del Dipartimento Clinico Sperimentale di Medicina e Farmacologia, Azienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, Italy

    L. Santarpia, F. Trimarchi & S. Benvenga MD

  2. Dipartimento di Pediatria, Azienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, Italy

    M. Valenzise, G. Di Pasquale, T. Arrigo, G. San Martino & F. De Luca

  3. Unità Operativa di Patologia Clinica, Centro di screening neonatale, Azienda Ospedaliera Papardo, Azienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, Italy

    M. P. Cicciò

  4. Programma Infradipartimentale di Endocrinologia Molecolare Clinica, Azienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, Italy

    S. Benvenga MD

  5. Master di Endocrinologia dell’Infanzia, dell’Adolescenza e della Donna, Università di Messina, Messina, Italy

    S. Benvenga MD

Authors
  1. L. Santarpia
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  2. M. Valenzise
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  3. G. Di Pasquale
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  4. T. Arrigo
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  5. G. San Martino
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  6. M. P. Cicciò
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  7. F. Trimarchi
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  8. F. De Luca
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  9. S. Benvenga MD
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Corresponding author

Correspondence to S. Benvenga MD.

Additional information

This article is dedicated to one of the Authors (Prof. Giuseppe Di Pasquale), gentleman and skilled geneticist, who suddenly died before the paper was published

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Santarpia, L., Valenzise, M., Di Pasquale, G. et al. TTF-2/FOXE1 gene polymorphisms in Sicilian patients with permanent primary congenital hypothyroidism. J Endocrinol Invest 30, 13–19 (2007). https://doi.org/10.1007/BF03347390

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  • DOI: https://doi.org/10.1007/BF03347390

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