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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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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.
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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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