Sex Chromosome Problems Discovered Through Prenatal Testing
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The Mutational Landscape of Myeloid Leukaemia in Down Syndrome
cancers Review The Mutational Landscape of Myeloid Leukaemia in Down Syndrome Carini Picardi Morais de Castro 1, Maria Cadefau 1,2 and Sergi Cuartero 1,2,* 1 Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, 08916 Badalona, Spain; [email protected] (C.P.M.d.C); [email protected] (M.C.) 2 Germans Trias i Pujol Research Institute (IGTP), Campus Can Ruti, 08916 Badalona, Spain * Correspondence: [email protected] Simple Summary: Leukaemia occurs when specific mutations promote aberrant transcriptional and proliferation programs, which drive uncontrolled cell division and inhibit the cell’s capacity to differentiate. In this review, we summarize the most frequent genetic lesions found in myeloid leukaemia of Down syndrome, a rare paediatric leukaemia specific to individuals with trisomy 21. The evolution of this disease follows a well-defined sequence of events and represents a unique model to understand how the ordered acquisition of mutations drives malignancy. Abstract: Children with Down syndrome (DS) are particularly prone to haematopoietic disorders. Paediatric myeloid malignancies in DS occur at an unusually high frequency and generally follow a well-defined stepwise clinical evolution. First, the acquisition of mutations in the GATA1 transcription factor gives rise to a transient myeloproliferative disorder (TMD) in DS newborns. While this condition spontaneously resolves in most cases, some clones can acquire additional mutations, which trigger myeloid leukaemia of Down syndrome (ML-DS). These secondary mutations are predominantly found in chromatin and epigenetic regulators—such as cohesin, CTCF or EZH2—and Citation: de Castro, C.P.M.; Cadefau, in signalling mediators of the JAK/STAT and RAS pathways. -
Adult Acute Myeloid Leukemia with Trisomy 11 As the Sole Abnormality
Letters to the Editor 2254 Adult acute myeloid leukemia with trisomy 11 as the sole abnormality is characterized by the presence of five distinct gene mutations: MLL-PTD, DNMT3A, U2AF1, FLT3-ITD and IDH2 Leukemia (2016) 30, 2254–2258; doi:10.1038/leu.2016.196 sequencing approach at the DNA level were also analyzed at the RNA level by visual inspection of the BAM files. The clinical characteristics and outcomes of 23 patients with Trisomy of chromosome 11 (+11) is the second most common sole +11 are summarized in Table 1. The patients were isolated trisomy in acute myeloid leukemia (AML) patients.1 The presence of +11 is associated with intermediate2,3 or poor 4–6 Table 1. Pretreatment clinical and molecular characteristics and patient outcomes. Whereas the clinical characteristics of solitary outcome of patients with acute myeloid leukemia (AML) and sole +11 +11 have been well established,4–6 relatively little is known about the mutational landscape of sole +11 AML in the age of next- Characteristica Sole +11 AML (n = 23) generation sequencing techniques that allow examination of multiple genes relevant to AML pathogenesis.6 So far, the most Age, years Median 71 common molecular feature in AML with isolated +11 is the – presence of a partial tandem duplication of the MLL (KMT2A) gene Range 25 84 (MLL-PTD), which is detectable in up to 90% of patients.7 Age group, n (%) Furthermore, a frequent co-occurrence of the FLT3 internal o60 years 18 (78) tandem duplication (FLT3-ITD) with MLL-PTD has been reported.8 ⩾ 60 years 5 (22) The aim of our study was to better characterize the mutational Female sex, n (%) 5 (22) landscape of adult AML patients with sole +11. -
ABC of Clinical Genetics CHROMOSOMAL DISORDERS II
ABC of Clinical Genetics CHROMOSOMAL DISORDERS II BMJ: first published as 10.1136/bmj.298.6676.813 on 25 March 1989. Downloaded from Helen M Kingston Developmental delay in Chromosomal abnormalities are generally associated with multiple child with deletion of congenital malformations and mental retardation. Children with more than chromosome 13. one physical abnormality, particularly ifretarded, should therefore undergo chromosomal analysis as part of their investigation. Chromosomal disorders are incurable but can be reliably detected by prenatal diagnostic techniques. Amniocentesis or chorionic villus sampling should be offered to women whose pregnancies are at increased risk-namely, women in their mid to late thirties, couples with an affected child, and couples in whom one partner carries a balanced translocation. Unfortunately, when there is no history of previous abnormality the risk in many affected pregnancies cannot be predicted beforehand. Autosomal abnormalities Parents Non-dysjunction Trisomy 21 (Down's syndrome) Down's syndrome is the commonest autosomal Gametes trisomy, the incidence in liveborn infants being one in 650, although more than half of conceptions with trisomy 21 do not survive to term. Affected children have a characteristic Offspring facial appearance, are mentally retarded, and Trisomy 21 often die young. They may have associated Non-dysjunction of chromosome 21 leading to Down's syndrome. congenital heart disease and are at increased risk recurrent for infections, atlantoaxial instability, http://www.bmj.com/ -- All chromosomal abnormalities at and acute leukaemia. They are often happy and 100 - ainniocentesis ---- Downl's syndrome at amniocentesis Risk for trisomy 21 in liveborn infants affectionate children who are easy to manage. -
The Prevalence of 47, XYY Males Among Collegiate Basketball Players
Western Michigan University ScholarWorks at WMU Master's Theses Graduate College 4-1976 The Prevalence of 47, XYY Males among Collegiate Basketball Players Joy Ann Price Follow this and additional works at: https://scholarworks.wmich.edu/masters_theses Part of the Genetics and Genomics Commons Recommended Citation Price, Joy Ann, "The Prevalence of 47, XYY Males among Collegiate Basketball Players" (1976). Master's Theses. 2377. https://scholarworks.wmich.edu/masters_theses/2377 This Masters Thesis-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Master's Theses by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. THE PREVALENCE OF 47,XYY MALES AMONG COLLEGIATE BASKETBALL PLAYERS by Joy Ann Price A Project Report Submitted to the Faculty of The Graduate College in partial fulfillment of the Specialist in Arts Degree Western Michigan University Kalamazoo, Michigan A p ri1 1976 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGEMENTS My appreciation and gratitude go to the members of my committee, Dr. Walter E. Johnson, Dr. Paul E. Holkeboer and Dr. Mary M. Rigney. My thanks go to them as veil as Dr. Rodney Cyrus of the University of Wisconsin-Oshkosh and Dr. W.J. Perreault of Lawrence University, whose advic encouragement and constructive criticism were most h e lp f u l. Finally, I would like to make a special note of gratitude to my husband, James H. Price, for his patience during the many ups and downs of this research. -
Dr. Fern Tsien, Dept. of Genetics, LSUHSC, NO, LA Down Syndrome
COMMON TYPES OF CHROMOSOME ABNORMALITIES Dr. Fern Tsien, Dept. of Genetics, LSUHSC, NO, LA A. Trisomy: instead of having the normal two copies of each chromosome, an individual has three of a particular chromosome. Which chromosome is trisomic determines the type and severity of the disorder. Down syndrome or Trisomy 21, is the most common trisomy, occurring in 1 per 800 births (about 3,400) a year in the United States. It is one of the most common genetic birth defects. According to the National Down Syndrome Society, there are more than 400,000 individuals with Down syndrome in the United States. Patients with Down syndrome have three copies of their 21 chromosomes instead of the normal two. The major clinical features of Down syndrome patients include low muscle tone, small stature, an upward slant to the eyes, a single deep crease across the center of the palm, mental retardation, and physical abnormalities, including heart and intestinal defects, and increased risk of leukemia. Every person with Down syndrome is a unique individual and may possess these characteristics to different degrees. Down syndrome patients Karyotype of a male patient with trisomy 21 What are the causes of Down syndrome? • 95% of all Down syndrome patients have a trisomy due to nondisjunction before fertilization • 1-2% have a mosaic karyotype due to nondisjunction after fertilization • 3-4% are due to a translocation 1. Nondisjunction refers to the failure of chromosomes to separate during cell division in the formation of the egg, sperm, or the fetus, causing an abnormal number of chromosomes. As a result, the baby may have an extra chromosome (trisomy). -
The Epidemiology of Sex Chromosome Abnormalities
Received: 12 March 2020 Revised: 11 May 2020 Accepted: 11 May 2020 DOI: 10.1002/ajmg.c.31805 RESEARCH REVIEW The epidemiology of sex chromosome abnormalities Agnethe Berglund1,2,3 | Kirstine Stochholm3 | Claus Højbjerg Gravholt2,3 1Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark Abstract 2Department of Molecular Medicine, Aarhus Sex chromosome abnormalities (SCAs) are characterized by gain or loss of entire sex University Hospital, Aarhus, Denmark chromosomes or parts of sex chromosomes with the best-known syndromes being 3Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Turner syndrome, Klinefelter syndrome, 47,XXX syndrome, and 47,XYY syndrome. Denmark Since these syndromes were first described more than 60 years ago, several papers Correspondence have reported on diseases and health related problems, neurocognitive deficits, and Agnethe Berglund, Department of Clinical social challenges among affected persons. However, the generally increased comor- Genetics, Aarhus University Hospital, Aarhus, Denmark. bidity burden with specific comorbidity patterns within and across syndromes as well Email: [email protected] as early death of affected persons was not recognized until the last couple of Funding information decades, where population-based epidemiological studies were undertaken. More- Familien Hede Nielsens Fond; Novo Nordisk over, these epidemiological studies provided knowledge of an association between Fonden, Grant/Award Numbers: NNF13OC0003234, NNF15OC0016474 SCAs and a negatively reduced socioeconomic status in terms of education, income, retirement, cohabitation with a partner and parenthood. This review is on the aspects of epidemiology in Turner, Klinefelter, 47,XXX and 47,XYY syndrome. KEYWORDS 47,XXX syndrome, 47,XYY syndrome, epidemiology, Klinefelter syndrome, Turner syndrome 1 | INTRODUCTION 100 participants, and many with much fewer participants. -
Cytogenetics, Chromosomal Genetics
Cytogenetics Chromosomal Genetics Sophie Dahoun Service de Génétique Médicale, HUG Geneva, Switzerland [email protected] Training Course in Sexual and Reproductive Health Research Geneva 2010 Cytogenetics is the branch of genetics that correlates the structure, number, and behaviour of chromosomes with heredity and diseases Conventional cytogenetics Molecular cytogenetics Molecular Biology I. Karyotype Definition Chromosomal Banding Resolution limits Nomenclature The metaphasic chromosome telomeres p arm q arm G-banded Human Karyotype Tjio & Levan 1956 Karyotype: The characterization of the chromosomal complement of an individual's cell, including number, form, and size of the chromosomes. A photomicrograph of chromosomes arranged according to a standard classification. A chromosome banding pattern is comprised of alternating light and dark stripes, or bands, that appear along its length after being stained with a dye. A unique banding pattern is used to identify each chromosome Chromosome banding techniques and staining Giemsa has become the most commonly used stain in cytogenetic analysis. Most G-banding techniques require pretreating the chromosomes with a proteolytic enzyme such as trypsin. G- banding preferentially stains the regions of DNA that are rich in adenine and thymine. R-banding involves pretreating cells with a hot salt solution that denatures DNA that is rich in adenine and thymine. The chromosomes are then stained with Giemsa. C-banding stains areas of heterochromatin, which are tightly packed and contain -
XYY Syndrome – Jacobs Syndrome
XYY Syndrome – Jacobs Syndrome XYY syndrome, sometimes known as Jacobs syndrome, is a sex chromosome aneuploidy that occurs in males when there are two copies of the Y chromosome instead of the expected one Y chromosome (figure 1). It is a chromosomal condition occurring in at least 1 in every 1000 male births; however, many males with XYY syndrome never come to clinical attention so it could be more common. Some males with XYY syndrome will be mosaic, where some of their cells have two Y chromosomes and the other cells have the usual one Y chromosome. Many babies that are born with XYY syndrome do not have any clinical features and symptoms. There are no fertility issues associated with XYY syndrome. Males with XYY syndrome can be very tall and may have severe acne during adolescence. The average intellectual capacity of males with XYY syndrome is within the normal range; however their IQ may be slightly lower than their siblings. Learning difficulties have been associated in some people with XYY syndrome, usually involving speech and language. There are many misconceptions about males with XYY syndrome, previously, it was sometimes called the super-male disease and was associated with being overly-aggressive and lacking in empathy. Recent studies have disproven this and they are no longer associated with XYY syndrome. What does a Non-invasive Prenatal Test (NIPT) result mean? Receiving a high probability result for XYY syndrome means that there is a significant chance that a baby will have XYY syndrome. However, NIPT is a screening test meaning in some rare instances, the baby may not actually have the condition. -
Double Aneuploidy in Down Syndrome
Chapter 6 Double Aneuploidy in Down Syndrome Fatma Soylemez Additional information is available at the end of the chapter http://dx.doi.org/10.5772/60438 Abstract Aneuploidy is the second most important category of chromosome mutations relat‐ ing to abnormal chromosome number. It generally arises by nondisjunction at ei‐ ther the first or second meiotic division. However, the existence of two chromosomal abnormalities involving both autosomal and sex chromosomes in the same individual is relatively a rare phenomenon. The underlying mechanism in‐ volved in the formation of double aneuploidy is not well understood. Parental ori‐ gin is studied only in a small number of cases and both nondisjunctions occurring in a single parent is an extremely rare event. This chapter reviews the characteristics of double aneuploidies in Down syndrome have been discussed in the light of the published reports. Keywords: Double aneuploidy, Down Syndrome, Klinefelter Syndrome, Chromo‐ some abnormalities 1. Introduction With the discovery in 1956 that the correct chromosome number in humans is 46, the new area of clinical cytogenetic began its rapid growth. Several major chromosomal syndromes with altered numbers of chromosomes were reported, such as Down syndrome (trisomy 21), Turner syndrome (45,X) and Klinefelter syndrome (47,XXY). Since then it has been well established that chromosome abnormalities contribute significantly to genetic disease resulting in reproductive loss, infertility, stillbirths, congenital anomalies, abnormal sexual development, mental retardation and pathogenesis of malignancy [1]. Clinical features of patients with common autosomal or sex chromosome aneuploidy is shown in Table 1. © 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. -
Paternally Inherited Trisomy at D21S11 and Mutation at DXS10135 Microsatellite Marker in a Case of Fetus Paternity Establishment
Egyptian Journal of Forensic Sciences (2015) xxx, xxx–xxx HOSTED BY Contents lists available at ScienceDirect Egyptian Journal of Forensic Sciences journal homepage: http://www.journals.elsevier.com/egyptian-journal-of-forensic-sciences CASE REPORT Paternally inherited trisomy at D21S11 and mutation at DXS10135 microsatellite marker in a case of fetus paternity establishment Pankaj Shrivastava a,*, Toshi Jain a,b, Sonia Kakkar c, Veena Ben Trivedi a a DNA Fingerprinting Unit, State Forensic Science Laboratory, Department of Home (Police), Govt. of Madhya Pradesh, Sagar 470001, MP, India b School of Studies in Microbiology, Jiwaji University, Gwalior, MP, India c Deptt of Forensic Medicine, PGIMER, Chandigarh, India Received 3 June 2015; revised 29 July 2015; accepted 6 September 2015 KEYWORDS Abstract The case of establishment of paternity of an aborted fetus was examined with 15 auto- DNA profiling; somal STR markers. The genotype of the fetus was X at amelogenin marker and showed inheritance D21S11; of both the alleles of father at D21S11 marker, thus displaying unusual tri-allelic pattern. The cases DXS10135; where mutation in any of biparental autosomal STR markers is observed, the use of additional STR X-STR; marker system is recommended. On testing all the three samples with 12 X-STR markers, all the Trisomy; maternal and paternal alleles were accounted in the female fetus except at DXS10135 marker. Mutation The genotypes of mother, fetus and father at DXS10135 were 20, 22; 20, 20 and 21, which confirmed mutation of the paternal allele in the female fetus. The paternal allele contracted from 21 to 20. The allele peak heights of D21S11 and DXS10135 markers were also examined to rule out the possibility of any false allele. -
©Ferrata Storti Foundation
Malignant Lymphomas original paper haematologica 2001; 86:71-77 Splenic marginal zone B-cell http://www.haematologica.it/2001_01/0071.htm lymphomas: two cytogenetic subtypes, one with gain of 3q and the other with loss of 7q FRANCESC SOLÉ,* MARTA SALIDO,* BLANCA ESPINET,* *Laboratori de Citologia Hematològica, Laboratori de Referència JUAN LUÍS GARCIA,° JOSÉ ANGEL MARTINEZ CLIMENT,# ISABEL de Catalunya, Departament de Patologia, Hospital del Mar, IMAS, GRANADA,@ JESÚS Mª HERNÁNDEZ,° ISABEL BENET,# MIGUEL IMIM, Barcelona; Escola de Citologia Hematològica Soledad ANGEL PIRIS,^ MANUELA MOLLEJO,§ PEDRO MARTINEZ,§ Woessner-IMAS; °Servicio de Hematología, Hospital Universitario TERESA VALLESPÍ,** ALICIA DOMINGO,°° SERGI SERRANO,* Centro de Investigación del Cáncer, Universidad de Salamanca- CSIC; #Servicio de Hematología y Oncología Médica, Hospital Clíni- SOLEDAD WOESSNER,* LOURDES FLORENSA* co Universitario de Valencia; @Servei d'Hematologia Hospital Ger- mans Trias i Pujol, Badalona; ^Programa de Patología Molecular, Centro Nacional de Investigaciones Oncológicas Carlos III, Madrid; §Servicio de Anatomia Patológica, Complejo Hospitalario de Tole- Correspondence: Francesc Solé, M.D., Laboratori de Citologia Hema- do; **Servicio de Hematología. Hospital Universitari Vall d'He- tològica, Laboratori de Referència de Catalunya, Departament de brón, Barcelona; °°Servicio de Hematología, Laboratorio de Patologia, Hospital del Mar, Passeig Maritim, 25-29, 08003 Barcelona, Spain. Phone: international +34-93-2211010 ext.1073 Fax: interna- Citología Hematológica, Ciudad Sanitaria y Universitaria de Bell- tional +34-93-2212920 - E-mail: [email protected] vitge, Hospital Princeps d’Espanya, Spain Background and Objectives. Splenic marginal zone B-cell plenic marginal zone B-cell lymphoma (SMZBCL) is lymphoma (SMZBCL) has clinical, immunophenotypic and a recognized entity for which the clinical, morpho- histologic features distinct from other B-cell malignancies, logic, immunophenotypic and histologic character- but few chromosome studies have been previously report- S 1-3 ed. -
Autism Spectrum Disorder Associated with 49,XYYYY: Case Report and Review of the Literature
Demily et al. BMC Medical Genetics (2017) 18:9 DOI 10.1186/s12881-017-0371-1 CASEREPORT Open Access Autism spectrum disorder associated with 49,XYYYY: case report and review of the literature Caroline Demily1*, Alice Poisson1, Elodie Peyroux1, Valérie Gatellier1, Alain Nicolas2, Caroline Rigard1, Caroline Schluth-Bolard3, Damien Sanlaville3 and Massimiliano Rossi3 Abstract Background: Sex chromosome aneuploidies occur in approximately one in 420 live births. The most frequent abnormalities are 45,X (Turner syndrome), 47,XXX (triple X), 47,XXY (Klinefelter syndrome), and 47,XYY. The prevalence of males with more than one extra sex chromosome (e.g. 48,XXYY or 48,XXXY) is less common. However, the literature provides little information about the cognitive and behavioural phenotype and the natural history of the disease. We report the clinical, neurocognitive, social cognitive and psychiatric characterization of a patient with 49,XYYYY syndrome. Case presentation: The patient presented with a complex phenotype including a particular cognitive profile with intellectual deficiency and autism spectrum disorder (ASD) with limited interests. Moreover, social anxiety disorder with selective mutism and separation anxiety disorder were observed (DSM-5 criteria, MINI Assessment). Conclusion: It is now admitted that 49,XYYYY has unique medical, neurodevelopmental and behavioural characteristics. Interestingly, ASD is more common in groups with Y chromosome aneuploidy. This clinical report suggests that understanding the cognitive and social functioning of these patients may provide new insights into possible therapeutic strategies, as cognitive remediation or social cognitive training. Keywords: XYYYY, Autism spectrum disorder, Social cognition, Neurocognition, Behavioural disorders Background 48,XYYY and 49,XYYYY karyotypes are very rare: less Sex chromosome aneuploidies (SCA) occur in approxi- than ten cases have been described for 48,XYYY and mately one in 420 live births [1].