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Genes Mar 2023An inverse comorbidity has been observed between Down syndrome (DS) and solid tumors such as breast and lung cancers, and it is posited that the overexpression of genes...
An inverse comorbidity has been observed between Down syndrome (DS) and solid tumors such as breast and lung cancers, and it is posited that the overexpression of genes within the Down Syndrome Critical Region (DSCR) of human chromosome 21 may account for this phenomenon. By analyzing publicly available DS mouse model transcriptomics data, we aimed to identify DSCR genes that may protect against human breast and lung cancers. Gene expression analyses with GEPIA2 and UALCAN showed that DSCR genes and are significantly downregulated in breast and lung cancers, and their expression levels are higher in triple-negative compared to luminal and HER2-positive breast cancers. KM Plotter showed that low levels of and are associated with poor survival outcomes in breast and lung cancers. Correlation analyses using OncoDB revealed that both genes are positively correlated in breast and lung cancers, suggesting that they are co-expressed and perhaps have complementary functions. Functional enrichment analyses using LinkedOmics also demonstrated that and expression correlates with T-cell receptor signaling, regulation of immunological synapses, TGF-β signaling, EGFR signaling, IFN-γ signaling, TNF signaling, angiogenesis, and the p53 pathway. Altogether, and may be essential for the development of breast and lung cancers. Experimental validation of their biological functions may further unravel their roles in DS and breast and lung cancers.
Topics: Mice; Animals; Humans; Down Syndrome; Transcription Factors; Signal Transduction; Lung Neoplasms
PubMed: 37107558
DOI: 10.3390/genes14040800 -
Mediators of Inflammation 2014Chemokines exert different inflammatory responses which can potentially be related to certain fetal chromosomal abnormalities. The aim of the study was to determine the...
OBJECTIVE
Chemokines exert different inflammatory responses which can potentially be related to certain fetal chromosomal abnormalities. The aim of the study was to determine the concentration of selected chemokines in plasma and amniotic fluid of women with fetal Down syndrome.
METHOD
Out of 171 amniocentesis, we had 7 patients with confirmed fetal Down syndrome (15th-18th weeks of gestation). For the purpose of our control, we chose 14 women without confirmed chromosomal aberration. To assess the concentration of chemokines in the blood plasma and amniotic fluid, we used a protein macroarray, which allows the simultaneous determination of 40 chemokines per sample.
RESULTS
We showed significant decrease in the concentration of 4 chemokines, HCC-4, IL-28A, IL-31, and MCP-2, and increase in the concentration of CXCL7 (NAP-2) in plasma of women with fetal Down syndrome. Furthermore, we showed decrease in concentration of 3 chemokines, ITAC, MCP-3, MIF, and increase in concentration of 4 chemokines, IP-10, MPIF-1, CXCL7, and 6Ckine, in amniotic fluid of women with fetal Down syndrome.
CONCLUSION
On the basis of our findings, our hypothesis is that the chemokines may play role in the pathogenesis of Down syndrome. Defining their potential as biochemical markers of Down syndrome requires further investigation on larger group of patients.
Topics: Adult; Amniocentesis; Amniotic Fluid; Biomarkers; Case-Control Studies; Chemokines; Down Syndrome; Female; Humans; Maternal Serum Screening Tests; Middle Aged; Pregnancy; Prenatal Diagnosis
PubMed: 25477715
DOI: 10.1155/2014/835837 -
Pediatric Pulmonology May 2021Airway anomalies are accountable for a substantial part of morbidity and mortality in children with Down syndrome (DS). Although tracheal anomalies occur more often in... (Review)
Review
INTRODUCTION
Airway anomalies are accountable for a substantial part of morbidity and mortality in children with Down syndrome (DS). Although tracheal anomalies occur more often in DS children, a structured overview on the topic is lacking. We systematically reviewed the characteristics of tracheal anomalies in DS children.
METHODS
A MEDLINE and EMBASE search for DS and tracheal anomalies was performed. Tracheal anomalies included tracheal stenosis, complete tracheal ring deformity (CTRD), tracheal bronchus, tracheomalacia, tracheal web, tracheal agenesis or atresia, laryngotracheoesophageal cleft type 3 or 4, trachea sleeve, and absent tracheal rings.
RESULTS
Fifty-nine articles were included. The trachea of DS children is significantly smaller than non-DS children. Tracheomalacia and tracheal bronchus are seen significantly more often in DS children. Furthermore, tracheal stenosis, CTRD, and tracheal compression by vascular structures are seen regularly in children with DS. These findings are reflected by the significantly higher frequency of tracheostomy and tracheoplasty performed in DS children.
CONCLUSION
In children with DS, tracheal anomalies occur more frequently and tracheal surgery is performed more frequently than in non-DS children. When complaints indicative of tracheal airway obstruction like biphasic stridor, dyspnea, or wheezing are present in children with DS, diagnostic rigid laryngotracheobronchoscopy with special attention to the trachea is indicated. Furthermore, imaging studies (computed tomography, magnetic resonance imaging, and ultrasound) play an important role in the workup of DS children with airway symptoms. Management depends on the type, number, and extent of tracheal anomalies. Surgical treatment seems to be the mainstay in severe cases.
Topics: Child; Down Syndrome; Humans; Infant; Larynx; Trachea; Tracheal Diseases; Tracheal Stenosis
PubMed: 33434377
DOI: 10.1002/ppul.25203 -
Annual Review of Pharmacology and... Jan 2022Those with Down syndrome (DS)-trisomy for chromosome 21-are routinely impacted by cognitive dysfunction and behavioral challenges in children and adults and Alzheimer's...
Those with Down syndrome (DS)-trisomy for chromosome 21-are routinely impacted by cognitive dysfunction and behavioral challenges in children and adults and Alzheimer's disease in older adults. No proven treatments specifically address these cognitive or behavioral changes. However, advances in the establishment of rodent models and human cell models promise to support development of such treatments. A research agenda that emphasizes the identification of overexpressed genes that contribute demonstrably to abnormalities in cognition and behavior in model systems constitutes a rational next step. Normalizing expression of such genes may usher in an era of successful treatments applicable across the life span for those with DS.
Topics: Aged; Animals; Disease Models, Animal; Down Syndrome; Female; Humans; Neurodegenerative Diseases; Pregnancy
PubMed: 34990205
DOI: 10.1146/annurev-pharmtox-041521-103641 -
American Journal of Human Genetics Nov 1985A matched case-control study of 100 mothers of Down syndrome children, 100 mothers of children with other defects (defect controls), and 100 mothers of children with no...
A matched case-control study of 100 mothers of Down syndrome children, 100 mothers of children with other defects (defect controls), and 100 mothers of children with no defects (normal controls) was carried out. All infants were born in upstate New York in 1980 and 1981. Matching was very close on maternal age for the normal controls but not for the defect controls. The risk ratios for the association of cigarette smoking around the time of conception with Down syndrome was 0.58 (90% confidence interval of 0.34-0.98) in the case-defect control comparison and 0.56 (90% confidence interval of 0.33-0.95) in the case-normal control comparison. Stratification by alcohol ingestion and maternal age did not abolish the negative trend to association. The results are contrary to that of an earlier study of others that found a positive association of older age and trisomy in spontaneous abortions. In fact, among mothers of Down syndrome cases over age 30 in this analysis, the risk ratio was lower than for younger mothers. (For case-normal control comparisons, the value was 0.39 [90% confidence interval of 0.17-0.87]). If not due to chance or confounding, the negative association in our data may be attributable to, among other factors, a selective effect of smoking upon survival or fertilizability of +21 gametes prior to conception or upon survival of +21 conceptuses after fertilization.
Topics: Congenital Abnormalities; Down Syndrome; Female; Humans; Infant, Newborn; New York; Pregnancy; Reference Values; Risk; Smoking
PubMed: 2934980
DOI: No ID Found -
Archives of Pathology & Laboratory... Mar 2020Transient abnormal myelopoiesis is a hematopoietic disorder that occurs in up to 10% of neonates with Down syndrome. It is characterized by leukocytosis and the presence... (Review)
Review
Transient abnormal myelopoiesis is a hematopoietic disorder that occurs in up to 10% of neonates with Down syndrome. It is characterized by leukocytosis and the presence of circulating blast cells harboring truncating mutations with variable multiorgan system involvement. Placental involvement of transient abnormal myelopoiesis is infrequently described. Placental examination and identifying features related to transient abnormal myelopoiesis could be one of the early, if not the only, means of diagnosis of this condition in affected stillbirths, premature infants, and a subset of asymptomatic neonates. This article provides an overview of the placental pathology in transient abnormal myelopoiesis with review of the literature, and also discusses the important differential diagnoses.
Topics: Down Syndrome; Female; GATA1 Transcription Factor; Humans; Infant, Newborn; Leukemoid Reaction; Mutation; Placenta; Pregnancy
PubMed: 30969155
DOI: 10.5858/arpa.2018-0248-RS -
Genetics in Medicine : Official Journal... Sep 2009Trisomy 21 or Down syndrome is a chromosomal disorder resulting from the presence of all or part of an extra Chromosome 21. It is a common birth defect, the most... (Review)
Review
Trisomy 21 or Down syndrome is a chromosomal disorder resulting from the presence of all or part of an extra Chromosome 21. It is a common birth defect, the most frequent and most recognizable form of mental retardation, appearing in about 1 of every 700 newborns. Although the syndrome had been described thousands of years before, it was named after John Langdon Down who reported its clinical description in 1866. The suspected association of Down syndrome with a chromosomal abnormality was confirmed by Lejeune et al. in 1959. Fifty years after the discovery of the origin of Down syndrome, the term "mongolism" is still inappropriately used; persons with Down syndrome are still institutionalized. Health problems associated with that syndrome often receive no or little medical care, and many patients still die prematurely in infancy or early adulthood. Nevertheless, working against this negative reality, community-based associations have lobbied for medical care and research to support persons with Down syndrome. Different Trisomy 21 research groups have already identified candidate genes that are potentially involved in the formation of specific Down syndrome features. These advances in turn may help to develop targeted medical treatments for persons with Trisomy 21. A review on those achievements is discussed.
Topics: Animals; Chromosomes, Human, Pair 21; Clinical Trials as Topic; Disease Models, Animal; Down Syndrome; Gene Dosage; Genotype; History, 20th Century; History, 21st Century; Humans; Mice; Phenotype; Trisomy
PubMed: 19636252
DOI: 10.1097/GIM.0b013e3181b2e34c -
Down's Syndrome, Research and Practice... Jul 2007Understanding number concepts and basic mathematical skills is important for many everyday activities in modern societies. Little is understood about the numeracy... (Review)
Review
Understanding number concepts and basic mathematical skills is important for many everyday activities in modern societies. Little is understood about the numeracy abilities of people with Down syndrome. At present, it appears that numeracy is an area of relative difficulty and that progress with more complex mathematical understanding is slow. However, some teaching approaches that seek to utilise certain relative strengths to communicate number concepts seem to be useful in practice. Further research is needed to define the precise difficulties experienced by children with Down syndrome and to evaluate teaching strategies.
Topics: Child; Down Syndrome; Humans; Mathematics; Teaching
PubMed: 17692181
DOI: 10.3104/updates.2031 -
Down's Syndrome, Research and Practice... Jul 2007Teeth grinding turns out to be no more common in children with Down syndrome than it is in other children and it reduces with age. These are reassuring findings as teeth...
Teeth grinding turns out to be no more common in children with Down syndrome than it is in other children and it reduces with age. These are reassuring findings as teeth grinding can be quite an annoying problem at home and at school.
Topics: Adolescent; Age Factors; Bruxism; Child; Child, Preschool; Down Syndrome; Female; Humans; Male; Surveys and Questionnaires
PubMed: 17692183
DOI: 10.3104/updates.2048 -
The Journal of Pediatrics Apr 2023
Topics: Humans; Quality Improvement; Down Syndrome; Quality Assurance, Health Care
PubMed: 36563898
DOI: 10.1016/j.jpeds.2022.12.018