title: Functional characterization of two novel mutations in TTF-1/NKX2.1 homeodomain in patients with benign hereditary chorea.
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.
authors.affiliation: Institute of Cell Biology and Neurobiology, National Council of Research, 00015 Monterotondo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Provenzano
authors.affiliation: Institute of Cell Biology and Neurobiology, National Council of Research, 00015 Monterotondo, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Zamboni
authors.affiliation: Institute of Translational Pharmacology, National Council of Research, 00100 Rome, Italy.
authors.forename: Liana
authors.initials: L
authors.lastname: Veneziano
authors.affiliation: Institute of Translational Pharmacology, National Council of Research, 00100 Rome, Italy.
authors.forename: Elide
authors.initials: E
authors.lastname: Mantuano
authors.affiliation: Molecular Neurogenetics Unit, IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
authors.affiliation: Child Neurology Dept, IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zorzi
authors.affiliation: Movement Disorders Unit, Neurology Department, Sant Pau Hospital and Biomedical Research Institute, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Pagonabarraga
authors.affiliation: Laboratory of Neurogenetics, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Paola
authors.initials: P
authors.lastname: Giunti
authors.affiliation: Institute of Cell Biology and Neurobiology, National Council of Research, 00015 Monterotondo, Italy. Electronic address: donato.civitareale@cnr.it.
authors.forename: Donato
authors.initials: D
authors.lastname: Civitareale
mesh_terms: D000328:Adult; D002648:Child; D002819:Chorea / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
keywords: Benign hereditary chorea; Brain–thyroid–lung syndrome; Genotype/phenotype correlation; Neurological disease; TTF-1/Nkx2.1