Corrigendum: One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: relation to chromosomal dosage.

[This corrects the article DOI: 10.3389/fmed.2022.

Zinc metabolism and its role in immunity status in subjects with trisomy 21: chromosomal dosage effect.

Introduction: Trisomy 21 (T21), which causes Down syndrome (DS), is the most common chromosomal aneuploidy in humankind and includes different clinical comorbidities, among which the alteration of the immune system has a heavy impact on patient's lives. A molecule with an important role in immune response is zinc and it is known that its concentration is significantly lower in children with T21. Different hypotheses were made about this metabolic alteration and one of the reasons might be the overexpression of superoxide dismutase 1 () gene, as zinc is part of the SOD1 active enzymatic center.

The functional roles of S-adenosyl-methionine and S-adenosyl-homocysteine and their involvement in trisomy 21.

The one-carbon metabolism pathway is involved in critical human cellular functions such as cell proliferation, mitochondrial respiration, and epigenetic regulation. In the homocysteine-methionine cycle S-adenosyl-methionine (SAM) and S-adenosyl-homocysteine (SAH) are synthetized, and their levels are finely regulated to ensure proper functioning of key enzymes which control cellular growth and differentiation. Here we review the main biological mechanisms involving SAM and SAH and the known related human diseases.

First clinical evidence that trimethylsulfonium can serve as a biomarker for the production of the signaling molecule hydrogen sulfide.

Background: Hydrogen sulfide (HS) is established as the third gaseous signaling molecule and is known to be overproduced in down syndrome (DS) due to the extra copy of the CBS gene on chromosome 21, which has been suggested to contribute to the clinical manifestation of this condition. We recently discovered trimethylsulfonium (TMS) in human urine and highlighted its potential as a selective methylation metabolite of endogenously produced HS, but the clinical utility of this novel metabolite has not been previously investigated. We hypothesize that the elevation of HS production in DS would be reflected by an elevation in the methylation product TMS.

Machine learning based analysis for intellectual disability in Down syndrome.

Down syndrome (DS) or trisomy 21 is the most common genetic cause of intellectual disability (ID), but a pathogenic mechanism has not been identified yet. Studying a complex and not monogenic condition such as DS, a clear correlation between cause and effect might be difficult to find through classical analysis methods, thus different approaches need to be used. The increased availability of big data has made the use of artificial intelligence (AI) and in particular machine learning (ML) in the medical field possible.

Partial trisomy 21 with or without highly restricted Down syndrome critical region (HR-DSCR): report of two new cases and reanalysis of the genotype-phenotype association.

Background: Down syndrome (DS) is caused by the presence of an extra copy of full or partial human chromosome 21 (Hsa21). Partial (segmental) trisomy 21 (PT21) is the duplication of only a delimited region of Hsa21 and can be associated or not to DS: the study of PT21 cases is an invaluable model for addressing genotype-phenotype correlation in DS. Previous works reported systematic reanalyses of 132 subjects with PT21 and allowed the identification of a 34-kb highly restricted DS critical region (HR-DSCR) as the minimal region whose duplication is shared by all PT21 subjects diagnosed with DS.

One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: Relation to chromosomal dosage.

Introduction: Down syndrome (DS) is the most common chromosomal disorder and it is caused by trisomy of chromosome 21 (Hsa21). Subjects with DS show a large heterogeneity of phenotypes and the most constant clinical features present are typical facies and intellectual disability (ID). Several studies demonstrated that trisomy 21 causes an alteration in the metabolic profile, involving among all the one-carbon cycle.

A reassessment of Jackson's checklist and identification of two Down syndrome sub-phenotypes.

Down syndrome (DS) is characterised by several clinical features including intellectual disability (ID) and craniofacial dysmorphisms. In 1976, Jackson and coll. identified a checklist of signs for clinical diagnosis of DS; the utility of these checklists in improving the accuracy of clinical diagnosis has been recently reaffirmed, but they have rarely been revised.

Cognitive profiles in children and adolescents with Down syndrome.

The Down syndrome (DS) phenotype is usually characterized by relative strengths in non-verbal skills and deficits in verbal processing, but high interindividual variability has been registered in the syndrome. The goal of this study was to explore the cognitive profile, considering verbal and non-verbal intelligence, of children and adolescents with DS, also taking into account interindividual variability. We particularly aimed to investigate whether this variability means that we should envisage more than one cognitive profile in this population.

Structural Characterization of the Highly Restricted Down Syndrome Critical Region on 21q22.13: New and Transcript Isoforms.

Down syndrome (DS) is caused by trisomy of chromosome 21 and it is the most common genetic cause of intellectual disability (ID) in humans. Subjects with DS show a typical phenotype marked by facial dysmorphisms and ID. Partial trisomy 21 (PT21) is a rare genotype characterized by the duplication of a delimited chromosome 21 (Hsa21) portion and it may or may not be associated with DS diagnosis.

Is the Age of Developmental Milestones a Predictor for Future Development in Down Syndrome?

Down Syndrome (DS) is the most common genetic alteration responsible for intellectual disability, which refers to deficits in both intellectual and adaptive functioning. According to this, individuals with Down Syndrome (DS) reach developmental milestones (e.g.

The transcriptome profile of human trisomy 21 blood cells.

Background: Trisomy 21 (T21) is a genetic alteration characterised by the presence of an extra full or partial human chromosome 21 (Hsa21) leading to Down syndrome (DS), the most common form of intellectual disability (ID). It is broadly agreed that the presence of extra genetic material in T21 gives origin to an altered expression of genes located on Hsa21 leading to DS phenotype. The aim of this study was to analyse T21 and normal control blood cell gene expression profiles obtained by total RNA sequencing (RNA-Seq).

One-carbon pathway and cognitive skills in children with Down syndrome.

This work investigates the role of metabolite levels in the intellectual impairment of subjects with Down syndrome (DS). Homocysteine, folate, vitamin B12, uric acid (UA), creatinine levels and MTHFR C677T genotype were analyzed in 147 subjects with DS. For 77 subjects, metabolite levels were correlated with cognitive tests.

Plasma metabolome and cognitive skills in Down syndrome.

Trisomy 21 (Down syndrome, DS) is the main human genetic cause of intellectual disability (ID). Lejeune hypothesized that DS could be considered a metabolic disease, and we found that subjects with DS have a specific plasma and urinary metabolomic profile. In this work we confirmed the alteration of mitochondrial metabolism in DS and also investigated if metabolite levels are related to cognitive aspects of DS.

Reference quantitative transcriptome dataset for adult .

is a nematode widely used in biology and genomics as a model organism. We provide an integrated, quantitative reference map for the transcriptome of whole, wild type Bristol N2 strain worms. The map has been obtained by meta-analysis of 110 gene expression profiles available in Gene Expression Omnibus (GEO) repository and integrated using the computational biology tool Transcriptome Mapper (TRAM).

Partial trisomy 21 map: Ten cases further supporting the highly restricted Down syndrome critical region (HR-DSCR) on human chromosome 21.

Background: Down syndrome (DS) is characterized by the presence of an extra full or partial human chromosome 21 (Hsa21). An invaluable model to define genotype-phenotype correlations in DS is the study of the extremely rare cases of partial (segmental) trisomy 21 (PT21), the duplication of only a delimited region of Hsa21 associated or not to DS. A systematic retrospective reanalysis of 125 PT21 cases described up to 2015 allowed the creation of the most comprehensive PT21 map and the identification of a 34-kb highly restricted DS critical region (HR-DSCR) as the minimal region whose duplication is shared by all PT21 subjects diagnosed with DS.

[Corrigendum] Analysis of a nanoparticle‑enriched fraction of plasma reveals miRNA candidates for Down syndrome pathogenesis.

After the publication of the above paper, the authors noted that the names of a couple of the authors listed on the paper were associated with the wrong affliation: Specifically, the eighth and ninth listed authors, Francesca Antonaros and Allison Piovesan, are located at DIMES at the University of Florence (fourth affiliation address), not at CSGI, the Research Center for Colloids and Nanoscience in Florence (third affliation address). Therefore, the author and affiliation details for this paper should have been presented as follows: ALESSANDRO SALVI1, MARIKA VEZZOLI2, SARA BUSATTO1, LUCIA PAOLINI1,3, TERESA FARANDA1, EDOARDO ABENI1, MARIA CARACAUSI4, FRANCESCA ANTONAROS4, ALLISON PIOVESAN4, CHIARA LOCATELLI5, GUIDO COCCHI5,6, GUALTIERO ALVISI7, GIUSEPPINA DE PETRO1, DORIS RICOTTA1, PAOLO BERGESE1,3 and ANNALISA RADEGHIERI1,3. 1Department of Molecular and Translational Medicine, University of Brescia; 2Unit of Biostatistics, Department of Molecular and Translational Medicine, University of Brescia, I‑25123 Brescia; 3CSGI, Research Center for Colloids and Nanoscience, Sesto Fiorentino, I‑50019 Florence; 4Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna; 5Neonatology Unit, St.

Human protein-coding genes and gene feature statistics in 2019.

Objective: A well-known limit of genome browsers is that the large amount of genome and gene data is not organized in the form of a searchable database, hampering full management of numerical data and free calculations. Due to the continuous increase of data deposited in genomic repositories, their content revision and analysis is recommended. Using GeneBase, a software with a graphical interface able to import and elaborate National Center for Biotechnology Information (NCBI) Gene database entries, we provide tabulated spreadsheets updated to 2019 about human nuclear protein-coding gene data set ready to be used for any type of analysis about genes, transcripts and gene organization.

Dataset of differential gene expression between total normal human thyroid and histologically normal thyroid adjacent to papillary thyroid carcinoma.

This article contains further data and information from our published manuscript [1]. We aim to identify significant transcriptome alterations of total normal human thyroid vs. histologically normal thyroid adjacent to papillary thyroid carcinoma.

Analysis of a nanoparticle‑enriched fraction of plasma reveals miRNA candidates for Down syndrome pathogenesis.

Down syndrome (DS) is caused by the presence of part or all of a third copy of chromosome 21. DS is associated with several phenotypes, including intellectual disability, congenital heart disease, childhood leukemia and immune defects. Specific microRNAs (miRNAs/miR) have been described to be associated with DS, although none of them so far have been unequivocally linked to the pathology.

MTHFR C677T polymorphism analysis: A simple, effective restriction enzyme-based method improving previous protocols.

Background: 5,10-Methylentetrahydrofolate reductase (MTHFR) C677T polymorphism is one of the most studied genetic variations in the human genome. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) is one of the most used techniques to characterize the point mutations in genomic sequences because of its suitability and low cost. The most widely used method for the MTHFR C677T polymorphism characterization was developed by Frosst et al.

On the length, weight and GC content of the human genome.

Objective: Basic parameters commonly used to describe genomes including length, weight and relative guanine-cytosine (GC) content are widely cited in absence of a primary source. By using updated data and original software we determined these values to the best of our knowledge as standard reference for the whole human nuclear genome, for each chromosome and for mitochondrial DNA. We also devised a method to calculate the relative GC content in the whole messenger RNA sequence set and in transcriptomes by multiplying the GC content of each gene by its mean expression level.

Human trisomy 21 fibroblasts rescue methotrexate toxic effect after treatment with 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate.

Trisomy 21 causes Down syndrome (DS), the most common human genetic disorder and the leading genetic cause of intellectual disability. The alteration of one-carbon metabolism was described as the possible metabolic cause of the intellectual disability development in subjects with DS. One of the biochemical pathways involved in the one-carbon group transfer is the folate cycle.

Integrated Quantitative Transcriptome Maps of Human Trisomy 21 Tissues and Cells.

Down syndrome (DS) is due to the presence of an extra full or partial chromosome 21 (Hsa21). The identification of genes contributing to DS pathogenesis could be the key to any rational therapy of the associated intellectual disability. We aim at generating quantitative transcriptome maps in DS integrating all gene expression profile datasets available for any cell type or tissue, to obtain a complete model of the transcriptome in terms of both expression values for each gene and segmental trend of gene expression along each chromosome.

Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism.

Down syndrome (DS) is caused by the presence of a supernumerary copy of the human chromosome 21 (Hsa21) and is the most frequent genetic cause of intellectual disability (ID). Key traits of DS are the distinctive facies and cognitive impairment. We conducted for the first time an analysis of the Nuclear Magnetic Resonance (NMR)-detectable part of the metabolome in plasma and urine samples, studying 67 subjects with DS and 29 normal subjects as controls selected among DS siblings.