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 journalArticle

1 Citation (Scopus)

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

Fingerprint

Chorea
Mutation
Genes
Missense Mutation
Hypothyroidism
Lung Diseases
Thyroid Gland
Chromosomes
Phenotype
Lung
thyroid nuclear factor 1
DNA

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Functional characterization of two novel mutations in TTF-1/NKX2.1 homeodomain in patients with benign hereditary chorea. / Provenzano, Claudia; Zamboni, Michela; Veneziano, Liana; Mantuano, Elide; Garavaglia, Barbara; Zorzi, Giovanna; Pagonabarraga, Javier; Giunti, Paola; Civitareale, Donato.

In: Journal of the Neurological Sciences, Vol. 360, 15.01.2016, p. 78-83.

Research output: Contribution to journalArticle

Provenzano, Claudia ; Zamboni, Michela ; Veneziano, Liana ; Mantuano, Elide ; Garavaglia, Barbara ; Zorzi, Giovanna ; Pagonabarraga, Javier ; Giunti, Paola ; Civitareale, Donato. / Functional characterization of two novel mutations in TTF-1/NKX2.1 homeodomain in patients with benign hereditary chorea. In: Journal of the Neurological Sciences. 2016 ; Vol. 360. pp. 78-83.
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