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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
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| {{DiseaseDisorder infobox | | | {{DiseaseDisorder infobox | |
| Name = Down syndrome | | | Name = Down syndrome | |
| ICD10 = {{ICD10|Q|90||q|90}} |
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| ICD9 = {{ICD9|758.0}} |
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| ICDO = |
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| Image = Drill.jpg <!--- Do not change this picture without discussing it in the Down syndrome discussion page. Because of continued vandalism, pictures will be immediately reverted. ---> | | | Image = Drill.jpg <!--- Do not change this picture without discussing it in the Down syndrome discussion page. Because of continued vandalism, pictures will be immediately reverted. ---> | |
| Caption = Boy with Down syndrome assembling a bookcase| | | Caption = Boy with Down syndrome assembling a bookcase| |
| OMIM = 190685 |
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| OMIM_mult = |
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| MedlinePlus = 000997 |
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| DiseasesDB = 3898 |
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| MeshID = D004314 |
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| }} | | }} |
| {{Down syndrome}} | | {{Down syndrome}} |
| {{CMG}}
| | '''For patient information, click [[Down syndrome (patient information)|here]]''' |
| ==Overview==
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| ==Genetic research==
| | {{CMG}} {{AE}} {{HK}} {{SH}} |
| {{main|Research of Down syndrome-related genes}} | |
| Down syndrome is “a developmental abnormality characterized by [[trisomy]] of human [[chromosome 21]] (Nelson 619). The extra copy of chromosome-21 leads to an over expression of certain [[genes]] located on chromosome-21.
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| Research by Arron ''et al'' shows that some of the [[phenotypes]] (displayed genetic characteristics), associated with Down Syndrome can be related to the dysregulation of gene-regulating proteins (596). The gene-regulating proteins bind to [[DNA]] and initiate certain segments of DNA to be replicated for the production of a certain protein (Arron ''et al''. 596). The gene-regulator in interest is called NFATc. Its activities are controlled by two proteins, DSCR1 and DYRK1A; these genes are located on chromosome-21 (Epstein 582). In people with Down Syndrome, these proteins have 1.5 times greater concentration than normal (Arron ''et al''. 597). The elevated levels of DSCR1 and DYRK1A mean that most of the NFATc is located in the [[cytoplasm]] rather than in the [[nucleus (cell)|nucleus]] promoting [[DNA replication]] which will produce vital proteins (Epstein 583).
| | {{SK}} Trisomy 21, trisomy 21 syndrome, mongolianism, mongolism, Down's syndrome baby |
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| This dysregulation was discovered by testing in [[transgenic]] mice. The mice had segments of their chromosomes duplicated to simulate a human chromosme-21 trisomy (Arron ''et al''. 597). A common characteristic of Down Syndrome is poor muscle tone, so a test involving the grip strength of the mice showed that the genetically modified mice had a significantly weaker grip (Arron ''et al''. 596). The mice squeezed a probe with a paw; the modified mice displayed a .2 Newton (measurement of force) weaker grip (Arron ''et al''. 596). Down syndrome is also characterized by increased socialization. Both modified and unmodified mice were observed for social interaction. The modified mice showed as many as 25% more interactions per time period as the unmodified mice (Arron ''et al''. 596).
| | ==[[Down syndrome overview|Overview]]== |
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| The genes that may be responsible for the phenotypes associated may be located proximal to 21q22.3. Testing by Olson et al, in transgenic mice show the duplicated genes presumed to cause the phenotypes are not enough to cause the exact features. While the mice had sections of multiple genes duplicated to approximate a human chromosome-21 triplication, they only showed slight craniofacial abnormalities (688-690). The transgenic mice were compared to mice that had no gene duplication by measuring distances on various points on their skeletal structure and comparing them to the normal mice (Olson ''et al''. 687). The exact characteristics of Down Syndrome were not observed, so more genes involved for Down Syndrome [[phenotypes]] have to be located elsewhere.
| | ==[[Down syndrome historical perspective|Historical Perspective]]== |
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| Reeves ''et al'', using 250 clones of chromosme-21 and specific gene markers, were able to map the gene in mutated bacteria. The testing had 99.7% coverage of the gene with 99.9995% accuracy due to multiple redundancies in the mapping techniques. In the study 225 genes were identified (311-313).
| | ==[[Down syndrome pathophysiology|Pathophysiology]]== |
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| The search for major genes that may be involved in Down syndrome symptoms is normally in the region 21q21–21q22.3. However, studies by Reeves ''et al''. show that 41% of the genes on chromosome-21 of have no functional purpose, and only 54% of functional genes have a known protein sequence. Functionality of genes was determined by a computer using [[exon]] prediction analysis (312). [[Exon]] sequence was obtained by the same procedures of the chromosome-21 mapping.
| | ==[[Down syndrome causes|Causes]]== |
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| Research has led to an understanding that two genes located on chromosome-21, that code for proteins that control gene regulators, DSCR1 and DYRK1A can be responsible for some of the phenotypes associated with [[Down Syndrome]]. DSCR1 and DYRK1A cannot be blamed outright for the symptoms; there are a lot of genes that have no known purpose. And further research is needed in order to treat Down Sydrome more effectively.
| | ==[[Down syndrome differential diagnosis|Differentiating Down syndrome from other Diseases]]== |
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| Recent use of [[genetically modified organism|transgenic]] [[mouse|mice]] to study specific genes in the Down syndrome critical region has yielded some results. [[Amyloid beta|APP]]<ref>{{OMIM|104760}}, gene [[Locus (genetics)|located]] at [[Chromosome 21 (human)|21]][http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?l104760 q21]. Retrieved on [[2006-12-05]].</ref> is an [[Amyloid beta]] A4 precursor protein. It is suspected to have a major role in cognitive difficulties.<ref>{{cite web |title=Down syndrome traced to one gene |publisher=''The Scientist'' |first=Chandra |last= Shekhar |url=http://www.the-scientist.com/news/display/23869/ |date=2006-07-06 |accessdate = 2006-07-11}}</ref> Another gene, ETS2<ref>{{OMIM|164740}}, located at [[Chromosome 21 (human)|21]] [http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?l164740 q22.3]. Retrieved on [[2006-12-05]].</ref> is Avian Erythroblastosis Virus E26 Oncogene Homolog 2. Researchers have "demonstrated that overexpression of ETS2 results in [[apoptosis]]. Transgenic mice overexpressing ETS2 developed a smaller thymus and lymphocyte abnormalities, similar to features observed in Down syndrome."<ref>{{cite web |author=OMIM, NIH |url=http://www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164740 |title=V-ETS Avian Erythroblastosis virus E26 Oncogene Homolog 2 |accessdate = 2006-06-29}}</ref>
| | ==[[Down syndrome epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==Sociological and cultural aspects== | | ==[[Down syndrome risk factors|Risk Factors]]== |
| [[Disability|Advocates]] for people with Down syndrome point to various factors, such as special education and parental support groups to make life easier for parents. There are also strides being made in education, housing, and social settings to create environments which are accessible and supportive to people with Down syndrome. In most developed countries, since the early twentieth century many people with Down syndrome were housed in institutions or colonies and excluded from society. However, since the early 1960s parents and their organizations (such as [http://www.mencap.org.uk/ MENCAP]), educators and other professionals have generally advocated a policy of inclusion,<ref>{{cite book |title=Inclusion |publisher=National Down Syndrome Society |url=http://www.ndss.org/index.php?option=com_content&task=view&id=1941&Itemid=236 |accessdate = 2006-05-21}}</ref> bringing people with any form of mental or physical disability into general society as much as possible. In many countries, people with Down syndrome are educated in the normal school system; there are increasingly higher-quality opportunities to mix special education with regular education settings. | |
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| Despite this change, reduced abilities of people with Down syndrome can pose a challenge to parents and families. Although living with family is preferable to institutionalization, people with Down syndrome often encounter patronizing attitudes and discrimination in the wider community.
| | ==[[Down syndrome screening|Screening]]== |
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| The first World Down Syndrome Day was held on 21 March 2006. The day and month were chosen to correspond with 21 and trisomy respectively. It was proclaimed by Down Syndrome International.<ref>{{cite web| url=http://www.worlddownsyndromeday.org|title=World Down Syndrome Day| accessdate = 2006-06-02}}</ref> In the United States, the National Down Syndrome Society observes Down Syndrome Month every October as "a forum for dispelling stereotypes, providing accurate information, and raising awareness of the potential of individuals with Down syndrome."<ref>[http://www.ndss.org/index.php?option=com_content&task=view&id=1962&Itemid=233 National Down Syndrome Society]</ref> In South Africa, Down Syndrome Awareness Day is held every October 20.<ref>[http://www.downsyndrome.org.za/main.aspx?artid=54 Down Syndrome South Africa]</ref>
| | ==[[Down syndrome natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| ==References == | | ==Diagnosis== |
| {{reflist|2}}
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| ==Sources==
| | [[Down syndrome history and symptoms|History and Symptoms]] | [[Down syndrome physical examination|Physical Examination]] | [[Down syndrome laboratory findings|Laboratory Findings]] | [[Down syndrome electrocardiogram|Electrocardiogram]] | [[Down syndrome x ray|X Ray]] | [[Down syndrome CT|CT]] | [[Down syndrome MRI|MRI]] | [[Down syndrome echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Down syndrome other imaging findings|Other Imaging Findings]] | [[Down syndrome other diagnostic studies|Other Diagnostic Studies]] |
| *Arron, Joseph R., et al. (2006). NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. ''Nature, 441'': 595-599.
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| *Epstein, Charles J. (2006). Critical Genes in Critical Region. ''Nature, 441'': 582-583.
| | ==Treatment== |
| * {{cite book
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| | last =Ganong
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| | first =W.J.
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| | year =2005
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| | title =Review of Medical Physiology
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| | publisher =Mc-Graw Hill
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| | location =New York
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| }}
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| *Nelson, David L., & Gibbs, Richard H. (2004). The Critical Region in Trisomy-21. ''Science, 306'': 619-621.
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| *Olson, L.E., Richtsmeier J.T., & Reeves R.H. (2004). A Chromosome-21 Critical Region Does Not Cause Specific Down Syndrome Phenotypes. ''Science, 306'': 687-690.
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| *Reeves, Roger H., et al. (2000). The DNA Sequence of Human Chromosome 21. ''Nature, 405'': 311-319.
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| * {{cite book
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| | last =Underwood
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| | first =J.C.E.
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| | year =2004
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| | title =General and Systematic Pathology
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| | publisher =Churchill Livingstone
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| | location =Edinburgh
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| }}
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| ==Bibliography==
| | [[Down syndrome medical therapy|Medical Therapy]] | [[Down syndrome surgery|Surgery]] | [[Down syndrome primary prevention|Primary Prevention]] | [[Down syndrome secondary prevention|Secondary Prevention]] | [[Down syndrome cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Down syndrome future or investigational therapies|Future or Investigational Therapies]] | [[Down syndrome sociological and cultural aspects|Sociological and Cultural Aspects]] |
| * {{cite book
| | * |
| | last =Beck
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| | first =M.N.
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| | year =1999
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| | title =Expecting Adam
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| | publisher =Berkley Books
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| | location =New York
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| }}
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| * {{cite book
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| | last =Buckley
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| | first =S.
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| | year =2000
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| | title =Living with Down Syndrome
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| | publisher =The Down Syndrome Educational Trust
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| | location =Portsmouth, UK
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| | url =http://books.google.com/books?id=__5wB08U2hMC
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| | isbn =1903806011
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| }}
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| * {{cite book
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| | last =Down Syndrome Research Foundation
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| | year =2005
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| | title =Bright Beginnings: A Guide for New Parents
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| | publisher =Down Syndrome Research Foundation
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| | location =Buckinghamshire, UK
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| | url =http://www.dsrf.co.uk/Reading_material/Bright_beginnings.htm
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| }}
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| * {{cite journal
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| | journal= Ment Retard Dev Disabil Res Rev
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| | year= 2007
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| | volume= 13
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| | issue= 3
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| | pages= 272–8
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| | title= Psychiatric and behavioral disorders in persons with Down syndrome
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| | author= Dykens EM
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| | doi= 10.1002/mrdd.20159
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| | pmid= 17910080
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| }}
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| * Hassold, T.J., D. Patterson, eds. (1999). ''Down Syndrome: A Promising Future, Together''. New York: Wiley Liss.
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| * {{cite book
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| | last =Kingsley
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| | first =J.
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| | coauthors =M. Levitz
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| | year =1994
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| | title =Count Us In: Growing up with Down Syndrome
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| | publisher =Harcourt Brace
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| | location =San Diego
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| }}
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| * Pueschel, S.M., M. Sustrova, eds. (1997). ''Adolescents with Down Syndrome: Toward a More Fulfilling Life''. Baltimore, MD: Paul H. Brookes.
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| * {{cite book
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| | last =Selikowitz
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| | first =M.
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| | edition =2nd edition
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| | year =1997
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| | title =Down Syndrome: The Facts
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| | publisher =Oxford University Press
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| | location =Oxford, UK
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| }}
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| * {{cite book
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| | last =Van Dyke
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| | first =D.C.
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| | coauthors =P.J. Mattheis, S. Schoon Eberly, J. Williams
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| | year =1995
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| | title =Medical and Surgical Care for Children with Down Syndrome
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| | publisher =Woodbine House
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| | location =Bethesda, MD
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| }}
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| * {{cite book | |
| | last =Zuckoff
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| | first =M.
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| | year =2002
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| | title =Choosing Naia: A Family's Journey
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| | publisher =Beacon Press
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| | location =New York
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| }}
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| {{Chromosomal abnormalities}} | | {{Chromosomal abnormalities}} |