Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21

Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.

Trisomy 21 with t(5; 11) Chromosomal Translocation as New Unfavorable Cytogenetic Abnormalities in Pediatric Acute Myeloid Leukemia Type M2: One Case Report of Nine-year Follow-up and Literature Review

We report one case of pediatric acute myeloid leukemia type 2（AML-M2） who presented with karyotypic aberration of trisomy 21 with the t（5;11） chromosomal translocation. The patient achieved complete remission after two cycles of chemotherapy of daunorubicin, cytarabine and etoposide. Then, follow-up cytogenetic analysis from bone marrow cell cultures demonstrated a normal karyotype of 46, XY. After 9 years, the patient relapsed and the karyotypic abnormalities of trisomy 21 with t（5;11） reappeared. It was concluded that trisomy 21 with t（5; 11） is a new unfavorable cytogenetic aberration in AML-M2.

Dynamic Balance in Children With Trisomy 21:A Pilot Study

At age 5,children with trisomy 21 have roughly 2 years of delayed motor development.We aimed to verify if children with trisomy 21(AD)(N=6,7.67±1.51 years)had a similar performance to children with a typical development(TD)(N=37,5.19±0.40 years old),in a playful motor action(to spin on herself until she cannot get more).On average,ADs gave less laps,for less time,spending more time per rotation,but without significant difference.Of the AD,one-third fell and rose to continue to spin;one-third stopped and resumed spinning(with intervals of 2.05±0.86s).Three ADs performed the action counterclockwise and the other three in clockwise direction.The results support the hypothesis that AD can perform the activity of spinning,with DT(significantly)younger,allowing to AD momentary pauses and conditions for their physical security.

Realizing the potential of exploiting human IPSCs and their derivatives in research of Down syndrome

Down syndrome(DS)is a genetic condition characterized by intellectual disability,delayed brain development,and early onset Alzheimer’s disease.The use of primary neural cells and tissues is important for understanding this disease,but there are ethical and practical issues,including availability from patients and experimental manipulability.Moreover,there are significant genetic and physiological differences between animal models and humans,which limits the translation of the findings in animal studies to humans.Advancements in induced pluripotent stem cells(iPSC)technology have revolutionized DS research by providing a valuable tool for studying the cellular and molecular pathologies associated with DS.Induced pluripotent stem cells derived from cells obtained from DS patients contain the patient’s entire genome including trisomy 21.Trisomic iPSCs as well as their derived cells or organoids can be useful for disease modeling,investigating the molecular mechanisms,and developing potential strategies for treating or alleviating DS.In this review,we focus on the use of iPSCs and their derivatives obtained from DS individuals and healthy humans for DS research.We summarize the findings from the past decade of DS studies using iPSCs and their derivatives.We also discuss studies using iPSC technology to investigate DS-associated genes(e.g.,APP,OLIG1,OLIG2,RUNX1,and DYRK1A)and abnormal phenotypes(e.g.,dysregulated mitochondria and leukemia risk).Lastly,we review the different strategies for mitigating the limitations of iPSCs and their derivatives,for alleviating the phenotypes,and for developing therapies.

Congenital leukemia: A case report and review of literature

BACKGROUND Acute leukemia in newborns is also known as neonatal or congenital leukemia(CL)and is a rare disease with an incidence rate of 1-5 per 1000000 live births.After birth,infants with CL exhibit infiltrative cutaneous nodules,hepatosplenomegaly,thrombocytopenia,and immature leukocytes in the peripheral blood.These symptoms are frequently accompanied by congenital abnormalities including trisomy 21,trisomy 9,trisomy 13,or Turner syndrome.Despite significant advances in disease management,the survival rate is approximately 25%at 2 years.CASE SUMMARY Here,we document a case of trisomy 21-related acute myeloid leukemia(AML)in a female neonate.The baby was sent to the neonatal intensive care unit because of anorexia,poor responsiveness,and respiratory distress.She was diagnosed with AML based on bone marrow aspiration and immunophenotyping.Genetic sequencing identified a mutation in the GATA1 gene.After receiving the diagnosis,the parents decided against medical care for their child,and the baby died at home on day 9 after birth.CONCLUSIONS The newborn infant was diagnosed with trisomy 21-related AML.Genetic sequencing identified a mutation in the GATA1 gene.The parents abandoned medical treatment for their infant after receiving the diagnosis,and the infant died at home on the 9th day after birth.

Second pregnancy of trisomy 21 in a mother with mosaicism

In the case of a previous offspring with trisomy 21, recurrence risk for Down syndrome is about 1%. It may be due to chance, but the possibility of germline mosaicism for trisomy 21 in one of the parents has important implications for the recurrence. Here we report a young healthy mother, who has a second pregnancy of trisomy 21.

Prevalence of pulmonary hypertension among children with Down syndrome:A systematic review and meta-analysis

BACKGROUND Pulmonary hypertension(PH)has serious short-and long-term consequences.PH is gaining increasing importance in high risk groups such as Down syndrome(DS)as it influences their overall survival and prognosis.Hence,there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management.AIM To determine the prevalence of PH in children with DS.METHODS The authors individually conducted a search of electronic databases manually(Cochrane library,PubMed,EMBASE,Scopus,Web of Science).Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion.The words used in the literature search were“pulmonary hypertension”and“pulmonary arterial hypertension”;“Down syndrome”and“trisomy 21”and“prevalence”.The data were analyzed by Comprehensive Meta-Analysis Software Version 2.Risk of bias assessment and STROBE checklist were used for quality assessment.RESULTS Of 1578 articles identified,17 were selected for final analysis.The pooled prevalence of PH in these studies was 25.5%.Subgroup analysis was carried out for age,gender,region,year of publication,risk of bias and etiology of PH.CONCLUSION This review highlights the increasing prevalence of PH in children with DS.It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management.Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.

Case Report:CD19-positive acute myeloblastic leukemia with trisomy 21 as a sole acquired karyotypic abnormality

We report that a 63-year-old Chinese female had acute myeloblastic leukemia （AML） in which trisomy 21 （＋21） was found as the sole acquired karyotypic abnormality. The blasts were positive for rnyeloperoxidase, and the immunophenotype was positive for cluster of differentiation 19 （CD19）, CD33, CD34, and human leukocyte antigens （HLA）-DR. The chromosomal analysis of bone marrow showed 47,XX,＋21 [2]/46,XX[ 18]. Fluorescent in situ hybridization （FISH） showed that three copies of AML1 were situated in separate chromosomes, and that t（8;21） was negative. The patient did not have any features of Down syndrome. A diagnosis of CD 19-positive AML-M5 was established with trisomy 21 as a sole acquired karyotypic abnormality. The patient did not respond well to chemotherapy and died three months after the diagnosis. This is the first reported case of CD19-positive AML with trisomy 21 as the sole cytogenetie abnormality. The possible prognostic significance of the finding in AML with ＋21 as the sole acquired karyotypic abnormality was discussed.

Daily Life and Planning for the Future of Ageing People with Down Syndrome: Results from a National Study on Caregivers

Background: Limited research concerns the study of continuity in the future of the physical and social status of elderly people with DS that is when people who take care of them will not be there anymore (“after we have gone”). Objective: From a biopsychosocial perspective, to investigate the daily life of ageing people with Down Syndrome over 45 years old in order to identify the most important issues in better planning for their future. Methods: A cross-sectional Italian national study was carried out. An ad hoc questionnaire was administered to formal and informal caregivers of aging people with Down Syndrome. Results: 136 family members and health professionals were involved. Most of the people with Down Syndrome live at home, attend a daily center and do many activities. Most of them had never worked and she/he is not at all autonomous. 25% of caregivers declared that, nowadays, there is not planning for the future, and 30.9% of participants who planned their future collected information when it occurred (e.g. when the parents pass away). Conclusions: The aging of people with DS requires attention to the planning of their future. In order to better plan, it is necessary to avoid programming “in emergency”, but for time, keeping in mind of the activities developed by the people, their abilities and all of the elements that have allowed them to live well up to a point of their life.

eHealth Management Platform for Screening and Prediction of Down’s Syndrome in the Republic of Panama

Through engineering projects, we have integrated software engineering, geographical information systems and HL7 standard to propose a model of an eHealth management platform for Down’s syndrome screening, replicable in all the country. It will use real time sample information acquired from the local population and will geographically reference this information in the territory of Panama for future research.

Prenatal diagnosis of Down syndrome using cell-free fetal DNA in amniotic fluid by quantitative fluorescent polymersase chain reaction

Backgroud Amniotic fluid （AF） supernatant contains cell-free fetal DNA （cffDNA） fragments.This study attempted to take advantage of cffDNA as a new material for prenatal diagnosis,which could be combined with simple quantitative fluorescent polymerase chain reaction （QF-PCR） to provide an ancillary method for the prenatal diagnosis of trisomy 21 syndrome.Methods AF supernatant samples were obtained from 27 women carrying euploid fetuses and 28 women carrying aneuploid fetuses with known cytogenetic karyotypes.Peripheral blood samples of the parents were collected at the same time.Short tandem repeat （STR） fragments on chromosome 21 were amplified by QF-PCR.Fetal condition and the parental source of the extra chromosome could be determined by the STR peaks.Results The sensitivity of the assay for the aneuploid was 93％ （26/28; confidence interval,CI：77％-98％） and the specificity was 100％ （26/26; CI：88％-100％）.The determination rate of the origin of the extra chromosome was 69％.The sensitivity and the specificity of the assay in the euploid were 100％ （27/27）.Conclusions Trisomy 21 can be prenatally diagnosed by the QF-PCR method in AF supernatant.This karyotype analysis method greatly reduces the requirement for the specimen size.It will be a benefit for early amniocentesis and could avoid pregnancy complications.The method may become an ancillary method for prenatal diagnosis of trisomy 21.