Article
Neurosciences
Zhen Li, Jenny A. A. Klein, Sanjeev Rampam, Ronni Kurzion, Natalie Baker Campbell, Yesha Patel, Tarik F. F. Haydar, Ella Zeldich
Summary: This study investigates the molecular processes underlying the intellectual disability in Down syndrome by using induced pluripotent stem cell (iPSC) lines to generate cortical spheroids that mimic brain development affected by trisomy 21. Single cell RNA sequencing reveals cell type-specific transcriptomic changes, particularly in excitatory neuron populations. The study highlights the importance of cell type-specific analyses within a defined genetic background for comprehensive evaluation of cellular phenotypes in Down syndrome.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Veronica Fabiola Moran-Barroso, Alicia Cervantes, Maria del Refugio Rivera-Vega, Adriana del Castillo-Moreno, Alejandra Moreno-Chacon, Estefania Mejia-Cauich, Laura Erendira Contreras-Ortiz, Fernando Fernandez-Ramirez
Summary: The patient presents a wide range of clinical manifestations mainly due to proximal trisomy 13q, with the phenotype modified by the presence of a free trisomy 13 cell line. It is proposed that the mosaicism in the patient may have originated from a trisomic zygote that underwent a failed trisomic rescue associated with chromothripsis, resulting in the cell line with partial 13q proximal trisomy, which could explain the long-term survival of the patient.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Cell & Tissue Engineering
Kaoru Takasaki, Sara S. Kumar, Alyssa Gagne, Deborah L. French, Stella T. Chou
Summary: Trisomy 21 (T21), also known as Down Syndrome (DS), is a common chromosomal disorder caused by an extra copy of chromosome 21. Transient myeloproliferative disorder (TMD) is a pre-leukemic condition that specifically occurs in newborns with DS and is characterized by a mutation in the GATA1 transcription factor. We have generated a pair of isogenic T21 cell lines derived from a patient with TMD, with the only difference being the status of GATA1. These iPSC lines have been characterized for their pluripotency, differentiation potential, and genomic stability, making them a valuable resource for studying hematopoietic diseases associated with T21.
STEM CELL RESEARCH
(2023)
Article
Medicine, General & Internal
Beatrice Vione, Giuseppe Ramacieri, Giacomo Zavaroni, Angela Piano, Giorgia La Rocca, Maria Caracausi, Lorenza Vitale, Allison Piovesan, Caterina Gori, Gian Luca Pirazzoli, Pierluigi Strippoli, Guido Cocchi, Luigi Corvaglia, Chiara Locatelli, Maria Chiara Pelleri, Francesca Antonaros
Summary: This study found specific alterations in the one-carbon cycle in individuals with Down syndrome, including abnormal concentrations of THF, SAM, and SAH. The relevance of these results for understanding the biology of intellectual impairment in Down syndrome is discussed, with the proposal of 5-methyl-THF as a potential candidate for clinical trials to restore the dysregulation of the one-carbon cycle and potentially improve cognitive skills.
FRONTIERS IN MEDICINE
(2022)
Article
Biology
Stephanie Springer, Eva Karner, Christof Worda, Maria Magdalena Grabner, Elisabeth Seidl-Mlczoch, Franco Laccone, Juergen Neesen, Anke Scharrer, Barbara Ulm
Summary: This retrospective cohort study evaluated pregnancies complicated by fetal congenital heart disease (CHD) and trisomies 13, 18, and 21. The study found a high rate of pregnancy termination among affected families, but relatively higher livebirth and survival rates among infants with trisomy 21.
Article
Pediatrics
Rebecca A. Saberi, Gareth P. Gilna, Blaire V. Slavin, Carlos T. Huerta, Walter A. Ramsey, Christopher F. O'Neil Jr, Eduardo A. Perez, Juan E. Sola, Chad M. Thorson
Summary: This study analyzed the clinical characteristics and outcomes of patients with Down syndrome and Hirschsprung disease. The results showed that patients with Down syndrome experienced delays in diagnosis, longer hospital stays for surgical patients, and a higher mortality rate.
JOURNAL OF PEDIATRIC SURGERY
(2022)
Article
Genetics & Heredity
Jakob Schuy, Jesper Eisfeldt, Maria Pettersson, Niloofar Shahrokhshahi, Mohsen Moslem, Daniel Nilsson, Niklas Dahl, Mansoureh Shahsavani, Anna Falk, Anna Lindstrand
Summary: Using induced pluripotent stem cells (iPSCs) from patients, researchers investigated the effects of partial monosomy on neural cells. RNA-Seq analysis revealed downregulation of multiple genes within the deleted region and global transcriptional dysregulation. A comparison with trisomy 21 cell lines showed opposite expression changes for genes on chromosome 21 and non-chromosome 21 genes.
FRONTIERS IN GENETICS
(2022)
Article
Obstetrics & Gynecology
Chih-Ping Chen, Shin-Wen Chen, Liang-Kai Wang, Schu-Rern Chern, Peih-Shan Wu, Fang-Tzu Wu, Yen-Ting Pan, Chen-Chi Lee, Li-Feng Chen, Chen-Wen Pan, Yun-Yi Chen, Wayseen Wang
Summary: This article presents a case of mosaic trisomy 21 detected prenatally, with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line. Through amniocentesis and subsequent tests, it was confirmed that this condition gradually decreased and disappeared after birth.
TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY
(2023)
Article
Cell Biology
Kourtney Sloan, Jared Thomas, Matthew Blackwell, Deanna Voisard, Eva Lana-Elola, Sheona Watson-Scales, Daniel L. Roper, Joseph M. Wallace, Elizabeth M. C. Fisher, Victor L. J. Tybulewicz, Randall J. Roper
Summary: This study investigates the effects of triplicated genes on mouse skeletal phenotypes and finds that they can both improve and worsen bone deficits.
DISEASE MODELS & MECHANISMS
(2023)
Article
Obstetrics & Gynecology
Chih-Ping Chen, Te-Yao Hsu, Schu-Rern Chern, Peih-Shan Wu, Shin -Wen Chen, Liang-Kai Wang, Fang-Tzu Wu, Yen -Ting Pan, Yun-Yi Chen, Wayseen Wang
Summary: We present a case of mosaic trisomy 21 in amniocentesis in a twin pregnancy that resulted in a favorable fetal outcome. The maternal uniparental disomy (UPD) 21 and postnatal decrease of the trisomy 21 cell line were also observed. This case highlights the transient and benign nature of mosaic trisomy 21 and emphasizes the importance of considering UPD 21.
TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY
(2023)
Article
Cell & Tissue Engineering
Vishi Sharma, Sunita Nehra, Nishant Singhal
Summary: Human-mouse chimeric models are important tools for developing in-vivo disease models. However, the in-vivo detection of human cells is limited. In order to facilitate in-vivo modeling of Down syndrome, we have generated stable AAVS1-EGFP isogenic pair of DS human iPSCs through zinc finger mediated genetic engineering. These reporter cell lines provide a valuable tool for tracking graft cell integration, differentiation, and distinction from host cells in-vivo.
STEM CELL RESEARCH
(2022)
Article
Cell Biology
Anna J. Moyer, Fabian-Xose Fernandez, Yicong Li, Donna K. Klinedinst, Liliana D. Florea, Yasuhiro Kazuki, Mitsuo Oshimura, Roger H. Reeves
Summary: Trisomy 21 and mutations in the Sonic hedgehog (SHH) signaling pathway lead to similar phenotypes, including cerebellar hypoplasia, craniofacial abnormalities, congenital heart defects, and Hirschsprung disease. Overexpression of human chromosome 21 genes disrupts normal SHH signaling during development and affects the phenotypes. By overexpressing 163 chromosome 21 genes in SHH-responsive mouse cell lines and analyzing cerebellar samples from Down syndrome mouse models, this study identified genes that upregulate or inhibit SHH signaling. The findings prioritize dosage-sensitive chromosome 21 genes for further studies and suggest potential therapeutic targets to ameliorate Down syndrome phenotypes.
DISEASE MODELS & MECHANISMS
(2023)
Article
Genetics & Heredity
Upamanyu Pal, Pinku Halder, Anirban Ray, Sumantra Sarkar, Supratim Dutta, Papiya Ghosh, Sujay Ghosh
Summary: In this study, variations in MCM9 were found to be associated with reduced recombination and nondisjunction of chromosome 21 during meiosis I in a maternal age-independent manner. These variants did not affect the position of chiasma formation. In Silico analyses suggested that some MCM9 variants may alter protein function due to amino acid substitution, as well as identified splice variants in MCM9. It is hypothesized that these polymorphisms predispose women to reduced recombination on chromosome 21 in oocytes at meiosis I, leading to the birth of a child with Down syndrome.
Article
Obstetrics & Gynecology
Chih-Ping Chen, Liang-Kai Wang, Fang-Tzu Wu, Yen-Ting Pan, Peih-Shan Wu, Wen-Lin Chen, Meng-Shan Lee, Wayseen Wang
Summary: We present a case report of a pregnant woman with high-level mosaic trisomy 21 who underwent amniocentesis and non-invasive prenatal testing (NIPT) for trisomy 21. The prenatal testing showed positive results for trisomy 21 at 12 weeks of gestation. Multiple amniocentesis procedures were performed throughout the pregnancy, revealing a progressive decrease of the trisomy 21 cell line. At 36 weeks of gestation, the woman developed acute fatty liver and intrauterine fetal death, but the delivered baby did not have Down syndrome phenotype. These findings suggest that high-level mosaic trisomy 21 detected by amniocentesis can be associated with a decrease in the trisomy 21 cell line during pregnancy and perinatal fetal mortality and maternal morbidity.
TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY
(2023)
Article
Neurosciences
Natalia Barraza-Nunez, Ramon Perez-Nunez, Belen Gaete-Ramirez, Alejandra Barrios-Garrido, Christian Arriagada, Karen Poksay, Varghese John, Jean-Vianney Barnier, Ana Maria Cardenas, Pablo Caviedes
Summary: Down syndrome (DS) is a genetic disorder characterized by trisomy of chromosome 21 and cognitive deficits. The overexpression of amyloid precursor protein (APP) in DS has been linked to neuronal dysfunction and cognitive deficit. In this study, using a neuronal cell line derived from a trisomy 16 mouse, an animal model of DS, it was observed that PAK hyperphosphorylation impairs neurite outgrowth and remodeling. Inhibition of PAK1 activity increased neurite length and stimulated the formation of new processes.
NEUROTOXICITY RESEARCH
(2023)
Review
Genetics & Heredity
Colleen Jackson-Cook
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2019)
Article
Biochemistry & Molecular Biology
Gee Su Yang, Xinlei Mi, Colleen K. Jackson-Cook, Angela R. Starkweather, Debra Lynch Kelly, Kellie J. Archer, Fei Zou, Debra E. Lyon
Article
Biochemistry & Molecular Biology
Timothy P. York, Shawn J. Latendresse, Colleen Jackson-Cook, Dana M. Lapato, Sara Moyer, Aaron R. Wolen, Roxann Roberson-Nay, Elizabeth K. Do, Susan K. Murphy, Catherine Hoyo, Bernard F. Fuemmeler, Jerome F. Strauss
Article
Oncology
Lilia Gheghiani, Lei Wang, Youwei Zhang, Xavier T. R. Moore, Jinglei Zhang, Steven C. Smith, Yijun Tian, Liang Wang, Kristi Turner, Colleen K. Jackson-Cook, Nitai D. Mukhopadhyay, Zheng Fu
Summary: Overexpression of Plk1 drives tumorigenesis by causing chromosomal instability and aneuploidy, and higher expression of PLK1 is associated with increased genome-wide copy-number alterations in multiple human cancers. These findings suggest potential therapeutic opportunities for CIN-positive cancers.
Article
Oncology
Joseph Gillam, Aida Catic, Prabakaran Paulraj, Justin Dalton, Guanhua Lai, Colleen Jackson-Cook, Scott Turner, Andrea Ferreira-Gonzalez, Elizabeth Barrie
Summary: This article describes a 19-month-old female patient who presented with left lower extremity pain and language regression, and was diagnosed with non-DS-AMKL. The patient's karyotype showed trisomy 3, and a fusion between CBFA2T3 and GLIS2 on chromosome 16 was observed.
GENES CHROMOSOMES & CANCER
(2022)
Article
Oncology
Areej A. Alhareeri, Kellie J. Archer, Han Fu, Debra E. Lyon, R. K. Elswick, Debra L. Kelly, Angela R. Starkweather, Lynne W. Elmore, Yahya A. Bokhari, Colleen K. Jackson-Cook
BREAST CANCER RESEARCH
(2020)
Review
Pediatrics
Cybil S. Stingl, Colleen Jackson-Cook, Natario L. Couser
CASE REPORTS IN PEDIATRICS
(2020)