Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome
Phelan-McDermid syndrome (PMS) is a multi-system disorder characterized by significant variability in clinical presentation. The genetic etiology is also variable with differing sizes of deletions in the chromosome 22q13 region and types of genetic abnormalities (e.g., terminal or interstitial delet...
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| creator | Srikanth, Sujata Jain, Lavanya Zepeda-Mendoza, Cinthya Cascio, Lauren Jones, Kelly Pauly, Rini DuPont, Barb Rogers, Curtis Sarasua, Sara Phelan, Katy Morton, Cynthia Boccuto, Luigi |
| description | Phelan-McDermid syndrome (PMS) is a multi-system disorder characterized by significant variability in clinical presentation. The genetic etiology is also variable with differing sizes of deletions in the chromosome 22q13 region and types of genetic abnormalities (e.g., terminal or interstitial deletions, translocations, ring chromosomes, or SHANK3 variants). Position effects have been shown to affect gene expression and function and play a role in the clinical presentation of various genetic conditions. This study employed a topologically associating domain (TAD) analysis approach to investigate position effects of chromosomal rearrangements on selected candidate genes mapped to 22q13 in 81 individuals with PMS. Data collected were correlated with clinical information from these individuals and with expression and metabolic profiles of lymphoblastoid cells from selected cases. The data confirmed TAD predictions for genes encompassed in the deletions and the clinical and molecular data indicated clear differences among individuals with different 22q13 deletion sizes. The results of the study indicate a positive correlation between deletion size and phenotype severity in PMS and provide evidence of the contribution of other genes to the clinical variability in this developmental disorder by reduced gene expression and altered metabolomics. |
| doi_str_mv | 10.1371/journal.pone.0253859 |
| format | Article |
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The genetic etiology is also variable with differing sizes of deletions in the chromosome 22q13 region and types of genetic abnormalities (e.g., terminal or interstitial deletions, translocations, ring chromosomes, or SHANK3 variants). Position effects have been shown to affect gene expression and function and play a role in the clinical presentation of various genetic conditions. This study employed a topologically associating domain (TAD) analysis approach to investigate position effects of chromosomal rearrangements on selected candidate genes mapped to 22q13 in 81 individuals with PMS. Data collected were correlated with clinical information from these individuals and with expression and metabolic profiles of lymphoblastoid cells from selected cases. The data confirmed TAD predictions for genes encompassed in the deletions and the clinical and molecular data indicated clear differences among individuals with different 22q13 deletion sizes. The results of the study indicate a positive correlation between deletion size and phenotype severity in PMS and provide evidence of the contribution of other genes to the clinical variability in this developmental disorder by reduced gene expression and altered metabolomics.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0253859</identifier><identifier>PMID: 34228749</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abnormalities ; Adolescent ; Alzheimer's disease ; Analysis ; Autism ; Biology and Life Sciences ; Child ; Child, Preschool ; Chromosome 22 ; Chromosome Deletion ; Chromosome Disorders - genetics ; Chromosome rearrangements ; Chromosome translocations ; Chromosomes ; Chromosomes, Human, Pair 22 - genetics ; Cohort Studies ; Deletion ; Developmental disabilities ; Diagnosis ; Etiology ; Female ; Gene expression ; Gene Rearrangement ; Genes ; Genetic abnormalities ; Genetic aspects ; Genetic Variation ; Genetics ; Gynecology ; Hospitals ; Humans ; Hypotheses ; Male ; Metabolism ; Metabolomics ; Nursing schools ; Obstetrics ; Patients ; Phelan-McDermid syndrome ; Phenotypes ; Physical Sciences ; Position effects ; Social Sciences ; Transcription factors ; Variability ; Womens health</subject><ispartof>PloS one, 2021-07, Vol.16 (7), p.e0253859</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Srikanth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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The results of the study indicate a positive correlation between deletion size and phenotype severity in PMS and provide evidence of the contribution of other genes to the clinical variability in this developmental disorder by reduced gene expression and altered metabolomics.</description><subject>Abnormalities</subject><subject>Adolescent</subject><subject>Alzheimer's disease</subject><subject>Analysis</subject><subject>Autism</subject><subject>Biology and Life Sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromosome 22</subject><subject>Chromosome Deletion</subject><subject>Chromosome Disorders - genetics</subject><subject>Chromosome rearrangements</subject><subject>Chromosome translocations</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 22 - genetics</subject><subject>Cohort Studies</subject><subject>Deletion</subject><subject>Developmental 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effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome</title><author>Srikanth, Sujata ; Jain, Lavanya ; Zepeda-Mendoza, Cinthya ; Cascio, Lauren ; Jones, Kelly ; Pauly, Rini ; DuPont, Barb ; Rogers, Curtis ; Sarasua, Sara ; Phelan, Katy ; Morton, Cynthia ; Boccuto, Luigi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c622t-b7962835cd33eebbfea8b6806fe3d08010484ea65ff55b3ea05fe523851dd4f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Abnormalities</topic><topic>Adolescent</topic><topic>Alzheimer's disease</topic><topic>Analysis</topic><topic>Autism</topic><topic>Biology and Life Sciences</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromosome 22</topic><topic>Chromosome Deletion</topic><topic>Chromosome Disorders - genetics</topic><topic>Chromosome rearrangements</topic><topic>Chromosome 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One</addtitle><date>2021-07-06</date><risdate>2021</risdate><volume>16</volume><issue>7</issue><spage>e0253859</spage><pages>e0253859-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Phelan-McDermid syndrome (PMS) is a multi-system disorder characterized by significant variability in clinical presentation. The genetic etiology is also variable with differing sizes of deletions in the chromosome 22q13 region and types of genetic abnormalities (e.g., terminal or interstitial deletions, translocations, ring chromosomes, or SHANK3 variants). Position effects have been shown to affect gene expression and function and play a role in the clinical presentation of various genetic conditions. This study employed a topologically associating domain (TAD) analysis approach to investigate position effects of chromosomal rearrangements on selected candidate genes mapped to 22q13 in 81 individuals with PMS. Data collected were correlated with clinical information from these individuals and with expression and metabolic profiles of lymphoblastoid cells from selected cases. The data confirmed TAD predictions for genes encompassed in the deletions and the clinical and molecular data indicated clear differences among individuals with different 22q13 deletion sizes. The results of the study indicate a positive correlation between deletion size and phenotype severity in PMS and provide evidence of the contribution of other genes to the clinical variability in this developmental disorder by reduced gene expression and altered metabolomics.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34228749</pmid><doi>10.1371/journal.pone.0253859</doi><tpages>e0253859</tpages><orcidid>https://orcid.org/0000-0003-2017-4270</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-07, Vol.16 (7), p.e0253859 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2548925915 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Abnormalities Adolescent Alzheimer's disease Analysis Autism Biology and Life Sciences Child Child, Preschool Chromosome 22 Chromosome Deletion Chromosome Disorders - genetics Chromosome rearrangements Chromosome translocations Chromosomes Chromosomes, Human, Pair 22 - genetics Cohort Studies Deletion Developmental disabilities Diagnosis Etiology Female Gene expression Gene Rearrangement Genes Genetic abnormalities Genetic aspects Genetic Variation Genetics Gynecology Hospitals Humans Hypotheses Male Metabolism Metabolomics Nursing schools Obstetrics Patients Phelan-McDermid syndrome Phenotypes Physical Sciences Position effects Social Sciences Transcription factors Variability Womens health |
| title | Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T12%3A54%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Position%20effects%20of%2022q13%20rearrangements%20on%20candidate%20genes%20in%20Phelan-McDermid%20syndrome&rft.jtitle=PloS%20one&rft.au=Srikanth,%20Sujata&rft.date=2021-07-06&rft.volume=16&rft.issue=7&rft.spage=e0253859&rft.pages=e0253859-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0253859&rft_dat=%3Cgale_plos_%3EA667602030%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2548925915&rft_id=info:pmid/34228749&rft_galeid=A667602030&rft_doaj_id=oai_doaj_org_article_f1e267b546f04ca790d99f80fd77785b&rfr_iscdi=true |