Functional study of a novel single deletion in the TITF1/NKX2.1 homeobox gene that produces congenital hypothyroidism and benign chorea but not pulmonary distress

The Journal of Clinical Endocrinology and Metabolism
Christian M MoyaPilar Santisteban

Abstract

We studied two sisters with congenital hypothyroidism and choreoathetosis but not respiratory distress. The aim of this study was to establish the genetic defect that causes this phenotype and study the molecular mechanisms of the pathology by means of functional analysis. Sequencing of DNA, expression vectors generation, EMSAs, transfections experiments as well as bioinformatics analysis were performed. We found a new single deletion (825delC) in one allele of the TITF1/NKX2.1 gene. The mutation located in the C-terminal domain generates a nonsense thyroid transcription factor 1 (TTF1) protein, with 22 amino less and rich in positive charges. This protein shows diminished binding to DNA, does not interfere with wild-type (wt) TTF1 binding, and fails to activate reporter genes harboring the thyroglobulin (Tg), thyroperoxidase (TPO), or surfactant protein B (SP-B) promoters. In addition, the mutant (mut) protein has a dominant-negative effect on the transcriptional activity of wt TTF1 in a promoter-specific manner, inhibiting the transcription of Tg and TPO but not of SP-B. Using a Gal4 reporter system, we demonstrate that the mut protein is not transcriptionally active and does not likely compete with the wild type for coactiva...Continue Reading

Citations

Mar 1, 2010·Pediatric Allergy, Immunology, and Pulmonology·Lawrence M Nogee
Sep 16, 2008·Thyroid : Official Journal of the American Thyroid Association·Alfonso Massimiliano FerraraPaolo Emidio Macchia
Feb 6, 2013·Thyroid : Official Journal of the American Thyroid Association·Immacolata Cristina NettorePaolo Emidio Macchia
Jun 12, 2010·Orphanet Journal of Rare Diseases·Maynika V Rastogi, Stephen H LaFranchi
Dec 15, 2010·Endocrine-related Cancer·Catherine OrySylvie Chevillard
Dec 14, 2011·Journal of Clinical Research in Pediatric Endocrinology·Jesús BarreiroManuel Pombo
Jun 15, 2010·Movement Disorders : Official Journal of the Movement Disorder Society·Elena SalvatoreGiuseppe De Michele
Jan 3, 2016·Journal of the Neurological Sciences·Claudia ProvenzanoDonato Civitareale
Oct 11, 2011·Journal of the Neurological Sciences·Katsuya NakamuraShu-ichi Ikeda
Feb 5, 2011·Parkinsonism & Related Disorders·Rivka InzelbergEva Gak
Sep 4, 2007·Journal of the Neurological Sciences·Claudia ProvenzanoDonato Civitareale
May 20, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Janine F FelixDick Tibboel
Aug 19, 2007·Movement Disorders : Official Journal of the Movement Disorder Society·Friedrich AsmusPatrick F Chinnery
Feb 5, 2008·Clinical Genetics·J T Wigle, D D Eisenstat
Aug 20, 2010·Clinical Endocrinology·Tina Di PalmaMariastella Zannini
Jun 25, 2015·Italian Journal of Pediatrics·Sara MontiAlessandra Cassio
Jan 11, 2012·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Catherine H Y YuSusan Fox
Mar 23, 2010·Molecular and Cellular Endocrinology·Lucia Montanelli, Massimo Tonacchera
Oct 29, 2014·Nature Reviews. Endocrinology·Lara P FernándezPilar Santisteban
Jan 3, 2018·The Journal of Clinical Endocrinology and Metabolism·Christian M MoyaJosé C Moreno
Jun 9, 2018·Thyroid : Official Journal of the American Thyroid Association·Hiroyuki ShinoharaTomonobu Hasegawa
Oct 30, 2008·The Journal of Clinical Endocrinology and Metabolism·Emilie MaquetJohnny Deladoëy
Feb 27, 2015·Journal of Pediatric Endocrinology & Metabolism : JPEM·Malgorzata Kumorowicz-CzochDorota Tylek-Lemanska
Aug 11, 2020·Journal of Neural Transmission·José Fidel Baizabal-Carvallo, Francisco Cardoso
Feb 7, 2009·Arquivos brasileiros de endocrinologia e metabologia·Helton E RamosRui M B Maciel
Oct 3, 2007·Cancer Research·Sergio Ruiz-LlorenteUNKNOWN Medullary Thyroid Carcinoma Clinical Group
Apr 17, 2021·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·Sohier S Abou El-EllaNaglaa Fathy Barseem
Mar 15, 2008·Development·Tonggong DuStewart A Anderson
Jan 23, 2014·Development·Michael Herriges, Edward E Morrisey

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.