Search results for "Homeobox protein Nkx-2.5"
showing 6 items of 6 documents
Sema3a plays a role in the pathogenesis of CHARGE syndrome
2018
CHARGE syndrome is an autosomal dominant malformation disorder caused by heterozygous loss of function mutations in the chromatin remodeler CHD7. Chd7 regulates the expression of Sema3a, which also contributes to the pathogenesis of Kallmann syndrome, a heterogeneous condition with the typical features hypogonadotropic hypogonadism and an impaired sense of smell. Both features are common in CHARGE syndrome suggesting that SEMA3A may provide a genetic link between these syndromes. Indeed, we find evidence that SEMA3A plays a role in the pathogenesis of CHARGE syndrome. First, Chd7 is enriched at the Sema3a promotor in neural crest cells and loss of function of Chd7 inhibits Sema3a expression…
A systematic variant screening in familial cases of congenital heart defects demonstrates the usefulness of molecular genetics in this field
2016
International audience; The etiology of congenital heart defect (CHD) combines environmental and genetic factors. So far, there were studies reporting on the screening of a single gene on unselected CHD or on familial cases selected for specific CHD types. Our goal was to systematically screen a proband of familial cases of CHD on a set of genetic tests to evaluate the prevalence of disease-causing variant identification. A systematic screening of GATA4, NKX2-5, ZIC3 and Multiplex ligation-dependent probe amplification (MLPA) P311 Kit was setup on the proband of 154 families with at least two cases of non-syndromic CHD. Additionally, ELN screening was performed on families with supravalvula…
Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes
2015
AbstractChronic arsenic exposure is associated with increased morbidity and mortality for cardiovascular diseases. Arsenic increases myocardial infarction mortality in young adulthood, suggesting that exposure during foetal life correlates with cardiac alterations emerging later. Here, we investigated the mechanisms of arsenic trioxide (ATO) cardiomyocytes disruption during their differentiation from mouse embryonic stem cells. Throughout 15 days of differentiation in the presence of ATO (0.1, 0.5, 1.0 μM) we analysed: the expression of i) marker genes of mesoderm (day 4), myofibrillogenic commitment (day 7) and post-natal-like cardiomyocytes (day 15); ii) sarcomeric proteins and their orga…
In silico characterization of an Iroquois family-related homeodomain protein.
2005
Homeobox genes have been demonstrated to play important roles during cancer differentiation and embryonic development. The subset of Iroquois-related homeobox genes (IRXs) have furthermore been. demonstrated to be involved in several embryonic developmental processes such as patterning of the anterior-posterior and dorso-ventral axis, as well as specific regions of the central nervous system, and differentiation of the otic vesicle, branchial epithelium, and limbs. We have characterized a novel homeodomain protein and corresponding gene by means of computational biology. Since the protein sequence displayed high similarity to the human IRX proteins, the newly identified homeodomain protein …
Tetralogy of Fallot as a Model to Study Cardiac Progenitor Cell Migration and Differentiation During Heart Development
2009
Tetralogy of Fallot (ToF) has long been considered a congenital disorder that occurs due to environmental alterations during gestation. Recently, several mutated genes have been discovered that are thought to be responsible for the malformations observed in ToF. These genetic mutations, which are microdeletions, are sporadic and are frequently also present in trisomy 21 patients. The ToF malformations can be lethal, but for the last 50 years, surgical repairs that place an artificial patch to repair the four features of ToF have improved the survival of patients with ToF. However, 0.5% to 6% of patients who survive after surgical repair of ToF die of sudden cardiac death caused by ventricul…
Mutations in the NKX2.5 Gene and the PAX8 Promoter in a Girl with Thyroid Dysgenesis
2011
Screening of the known candidate genes involved in thyroid organogenesis has revealed mutations in a small subset of patients with congenital hypothyroidism due to thyroid dysgenesis (TD).We studied a girl with TD who had mutations in two transcription factors involved in thyroid development.Sequencing analysis of candidate genes involved in thyroid gland development revealed a new paternally inherited heterozygous mutation in the NKX2.5 gene (S265R) and a new maternally inherited heterozygous mutation in the PAX8 promoter region (-456CT). Both parents and a brother, who was also heterozygous for both mutations, were phenotypically normal. Immunofluorescence microscopy showed a correct nucl…