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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259982/ https://www.ncbi.nlm.nih.gov/pubmed/34228749 http://dx.doi.org/10.1371/journal.pone.0253859 |
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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_facet | 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 | Srikanth, Sujata |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8259982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82599822021-07-19 Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome 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 PLoS One Research Article 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. Public Library of Science 2021-07-06 /pmc/articles/PMC8259982/ /pubmed/34228749 http://dx.doi.org/10.1371/journal.pone.0253859 Text en © 2021 Srikanth et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article 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 Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome |
title | Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome |
title_full | Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome |
title_fullStr | Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome |
title_full_unstemmed | Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome |
title_short | Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome |
title_sort | position effects of 22q13 rearrangements on candidate genes in phelan-mcdermid syndrome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259982/ https://www.ncbi.nlm.nih.gov/pubmed/34228749 http://dx.doi.org/10.1371/journal.pone.0253859 |
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