Functional characterization of two novel mutations in TTF-1/NKX2.1 homeodomain in patients with benign hereditary chorea

Claudia Provenzano, Michela Zamboni, Liana Veneziano, Elide Mantuano, Barbara Garavaglia, Giovanna Zorzi, Javier Pagonabarraga, Paola Giunti, Donato Civitareale

Research output: Contribution to journalArticlepeer-review

Abstract

The thyroid transcription factor 1 (TTF-1) is encoded, on chromosome 14q13, by the gene termed TITF-1/NKX2.1. Mutations in this gene have been associated with chorea, hypothyroidism, and lung disease, all included in the "brain-thyroid-lung syndrome." We here describe two cases of novel missense mutations [NM-003317.3:c.516G > T and c.623G > C resulting in p.(Gln172His) and p.(Trp208Ser), respectively] in TITF-1/NKX2-1 in non-consanguineous patients. We provide a functional study of the role of the two mutations on the TTF-1 ability to bind DNA and to trans-activate both thyroid and lung specific gene promoters. Our results confirm the difficulty to correlate the TTF-1 activity with the clinical phenotype of affected patients and highlight the need to increase the limited knowledge we have on the activity of TTF-1 in neuronal cells.

Original languageEnglish
Pages (from-to)78-83
Number of pages6
JournalJournal of the Neurological Sciences
Volume360
DOIs
Publication statusPublished - Jan 15 2016

Keywords

  • Benign hereditary chorea
  • Brain-thyroid-lung syndrome
  • Genotype/phenotype correlation
  • Neurological disease
  • TTF-1/Nkx2.1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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