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Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor
Phelan–McDermid syndrome (PMS), caused by pathogenic variants in the SHANK3 gene or 22q13 deletions, is characterized by intellectual disability, autistic features, developmental delays, and neonatal hypotonia. Insulin-like growth factor 1 (IGF-1) and human growth hormone (hGH) have been shown to re...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956088/ https://www.ncbi.nlm.nih.gov/pubmed/36833418 http://dx.doi.org/10.3390/genes14020490 |
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author | Moffitt, Bridgette A. Sarasua, Sara M. Ivankovic, Diana Ward, Linda D. Valentine, Kathleen Bennett, William E. Rogers, Curtis Phelan, Katy Boccuto, Luigi |
author_facet | Moffitt, Bridgette A. Sarasua, Sara M. Ivankovic, Diana Ward, Linda D. Valentine, Kathleen Bennett, William E. Rogers, Curtis Phelan, Katy Boccuto, Luigi |
author_sort | Moffitt, Bridgette A. |
collection | PubMed |
description | Phelan–McDermid syndrome (PMS), caused by pathogenic variants in the SHANK3 gene or 22q13 deletions, is characterized by intellectual disability, autistic features, developmental delays, and neonatal hypotonia. Insulin-like growth factor 1 (IGF-1) and human growth hormone (hGH) have been shown to reverse neurobehavioral deficits in PMS. We assessed the metabolic profiling of 48 individuals with PMS and 50 controls and determined subpopulations by taking the top and bottom 25% of responders to hGH and IGF-1. A distinct metabolic profile for individuals with PMS showed a reduced ability to metabolize major energy sources and a higher metabolism of alternative energy sources. The analysis of the metabolic response to hGH or IGF-1 highlighted a major overlap between both high and low responders, validating the model and suggesting that the two growth factors share many target pathways. When we investigated the effect of hGH and IGF-1 on the metabolism of glucose, the correlation between the high-responder subgroups showed less similarity, whereas the low-responders were still relatively similar. Classification of individuals with PMS into subgroups based on responses to a compound can allow an investigation into pathogenic mechanisms, the identification of molecular biomarkers, an exploration of in vitro responses to candidate drugs, and eventually the selection of better candidates for clinical trials. |
format | Online Article Text |
id | pubmed-9956088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99560882023-02-25 Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor Moffitt, Bridgette A. Sarasua, Sara M. Ivankovic, Diana Ward, Linda D. Valentine, Kathleen Bennett, William E. Rogers, Curtis Phelan, Katy Boccuto, Luigi Genes (Basel) Article Phelan–McDermid syndrome (PMS), caused by pathogenic variants in the SHANK3 gene or 22q13 deletions, is characterized by intellectual disability, autistic features, developmental delays, and neonatal hypotonia. Insulin-like growth factor 1 (IGF-1) and human growth hormone (hGH) have been shown to reverse neurobehavioral deficits in PMS. We assessed the metabolic profiling of 48 individuals with PMS and 50 controls and determined subpopulations by taking the top and bottom 25% of responders to hGH and IGF-1. A distinct metabolic profile for individuals with PMS showed a reduced ability to metabolize major energy sources and a higher metabolism of alternative energy sources. The analysis of the metabolic response to hGH or IGF-1 highlighted a major overlap between both high and low responders, validating the model and suggesting that the two growth factors share many target pathways. When we investigated the effect of hGH and IGF-1 on the metabolism of glucose, the correlation between the high-responder subgroups showed less similarity, whereas the low-responders were still relatively similar. Classification of individuals with PMS into subgroups based on responses to a compound can allow an investigation into pathogenic mechanisms, the identification of molecular biomarkers, an exploration of in vitro responses to candidate drugs, and eventually the selection of better candidates for clinical trials. MDPI 2023-02-15 /pmc/articles/PMC9956088/ /pubmed/36833418 http://dx.doi.org/10.3390/genes14020490 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Moffitt, Bridgette A. Sarasua, Sara M. Ivankovic, Diana Ward, Linda D. Valentine, Kathleen Bennett, William E. Rogers, Curtis Phelan, Katy Boccuto, Luigi Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor |
title | Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor |
title_full | Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor |
title_fullStr | Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor |
title_full_unstemmed | Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor |
title_short | Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor |
title_sort | stratification of a phelan–mcdermid syndrome population based on their response to human growth hormone and insulin-like growth factor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956088/ https://www.ncbi.nlm.nih.gov/pubmed/36833418 http://dx.doi.org/10.3390/genes14020490 |
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