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Diagnostics (Basel, Switzerland) Aug 2023Non-invasive prenatal testing was first discovered in 1988; it was primarily thought to be able to detect common aneuploidies, such as Patau syndrome (T13), Edward... (Review)
Review
Non-invasive prenatal testing was first discovered in 1988; it was primarily thought to be able to detect common aneuploidies, such as Patau syndrome (T13), Edward Syndrome (T18), and Down syndrome (T21). It comprises a simple technique involving the analysis of cell-free foetal DNA (cffDNA) obtained through maternal serum, using advances in next-generation sequencing. NIPT has shown promise as a simple and low-risk screening test, leading various governments and private organizations worldwide to dedicate significant resources towards its integration into national healthcare initiatives as well as the formation of consortia and research studies aimed at standardizing its implementation. This article aims to review the reliability of NIPT while discussing the current challenges prevalent among different communities worldwide.
PubMed: 37568933
DOI: 10.3390/diagnostics13152570 -
Haematologica Oct 2023Children with Down syndrome (DS, trisomy 21) are at a significantly higher risk of developing acute leukemia compared to the overall population. Many studies... (Review)
Review
Children with Down syndrome (DS, trisomy 21) are at a significantly higher risk of developing acute leukemia compared to the overall population. Many studies investigating the link between trisomy 21 and leukemia initiation and progression have been conducted over the last two decades. Despite improved treatment regimens and significant progress in iden - tifying genes on chromosome 21 and the mechanisms by which they drive leukemogenesis, there is still much that is unknown. A focused group of scientists and clinicians with expertise in leukemia and DS met in October 2022 at the Jérôme Lejeune Foundation in Paris, France for the 1st International Symposium on Down Syndrome and Leukemia. This meeting was held to discuss the most recent advances in treatment regimens and the biology underlying the initiation, progression, and relapse of acute lymphoblastic leukemia and acute myeloid leukemia in children with DS. This review provides a summary of what is known in the field, challenges in the management of DS patients with leukemia, and key questions in the field.
Topics: Child; Humans; Down Syndrome; Leukemia, Myeloid, Acute; Acute Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; France
PubMed: 37439336
DOI: 10.3324/haematol.2023.283225 -
Science (New York, N.Y.) Aug 2023Most cancers exhibit aneuploidy, but its functional significance in tumor development is controversial. Here, we describe ReDACT (Restoring Disomy in Aneuploid cells...
Most cancers exhibit aneuploidy, but its functional significance in tumor development is controversial. Here, we describe ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting), a set of chromosome engineering tools that allow us to eliminate specific aneuploidies from cancer genomes. Using ReDACT, we created a panel of isogenic cells that have or lack common aneuploidies, and we demonstrate that trisomy of chromosome 1q is required for malignant growth in cancers harboring this alteration. Mechanistically, gaining chromosome 1q increases the expression of and suppresses p53 signaling, and we show that mutations are mutually exclusive with 1q aneuploidy in human cancers. Thus, tumor cells can be dependent on specific aneuploidies, raising the possibility that these "aneuploidy addictions" could be targeted as a therapeutic strategy.
Topics: Humans; Cell Cycle Proteins; Mutation; Neoplasms; Oncogenes; Proto-Oncogene Proteins; Trisomy; Gene Editing; Tumor Suppressor Protein p53; Carcinogenesis
PubMed: 37410869
DOI: 10.1126/science.adg4521 -
Revista Medica Del Instituto Mexicano... Sep 2023Down syndrome (DS) is the most common autosomal aneuploidy and the leading cause of intellectual disability of genetic origin worldwide. It is identified as a syndrome... (Review)
Review
Down syndrome (DS) is the most common autosomal aneuploidy and the leading cause of intellectual disability of genetic origin worldwide. It is identified as a syndrome in which the variability of its clinical manifestations and the severity of its phenotype have a multifactorial origin. Worldwide prevalence ranges between 1 per 700 live births and several factors that may be involved in the origin of DS have been proposed. Our objective was to describe updates regarding risk factors in the cytogenetic origin or cause of DS. We conducted a narrative review study in which a literature search was carried out from January to June 2022 in databases such as PubMed, EBSCO, Medigraphic, ClinicalKey, and meta-search engines such as Elsevier and Evidence Alerts. Only articles published in the last 10 years in English and Spanish were included. The search terms used were: Down syndrome, risk factors, prevention. Although DS is a very common chromosomal pathology worldwide, there is no single risk factor at the origin of meiotic or mitotic nondisjunction of chromosome 21, but rather each of the associated risk factors contributes to a greater or lesser degree to a cytogenetic predisposition in the etiology of trisomy 21. During the review it was identified that the main established risk factor associated with DS is still advanced maternal age (≥ 35 years).
Topics: Adult; Humans; Down Syndrome; Maternal Age; Nondisjunction, Genetic; Risk Factors; Female
PubMed: 37769135
DOI: 10.5281/zenodo.8316459 -
Endocrine Connections Aug 2023The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility... (Review)
Review
The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility aspects of the sex chromosome trisomies, XXY, XYY, and XXX, with special reference to the karyotype 45,X/47,XXX. Each has a 'specific' (but variable) phenotype but may be modified by mosaicism. Although the alterations in the hypothalamic-pituitary-gonadal axis are important (and discussed), the emphasis here is on potential fertility and if one might predict that at various epochs within an individual's life span: fetal, 'mini'-puberty, childhood, puberty, and adulthood. The reproductive axis is often affected in females with the 47,XXX karyotype with diminished ovarian reserve and accelerated loss of ovarian function. Fewer than 5% of females with Turner syndrome have the 45,X/47,XXX karyotype. They have taller stature and less severe fertility issues compared to females with the 45,X or other forms of Turner syndrome mosaicism. For the 47,XXY karyotype, non-obstructive azoospermia is almost universal with sperm retrieval by micro-testicular sperm extraction possible in slightly fewer than half of the men. Men with the 47,XYY karyotype have normal to large testes and much less testicular dysfunction than those with the 47,XXY karyotype. They do have a slight increase in infertility compared to the reference population but not nearly as severe as those with the 47,XXY karyotype. Assisted reproductive technology, especially micro-testicular sperm extraction, has an important role, especially for those with 47,XXY; however, more recent data show promising techniques for the in vitro maturation of spermatogonial stem cells and 3D organoids in culture. Assisted reproductive technology is more complex for the female, but vitrification of oocytes has shown promising advances.
PubMed: 37399523
DOI: 10.1530/EC-22-0440