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.

Cross-sectional developmental trajectories in the adaptive functioning of children and adolescents with Down syndrome.

Background: Persons with Down syndrome (DS) reveal adaptive functioning (AF) difficulties. Studies on AF in DS have focused mainly on describing the profile (i.e.

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.

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.