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 <i>SHANK3</i> 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) ha...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/2/490 |
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| author | Bridgette A. Moffitt Sara M. Sarasua Diana Ivankovic Linda D. Ward Kathleen Valentine William E. Bennett Curtis Rogers Katy Phelan Luigi Boccuto |
| author_facet | Bridgette A. Moffitt Sara M. Sarasua Diana Ivankovic Linda D. Ward Kathleen Valentine William E. Bennett Curtis Rogers Katy Phelan Luigi Boccuto |
| author_sort | Bridgette A. Moffitt |
| collection | DOAJ |
| description | Phelan–McDermid syndrome (PMS), caused by pathogenic variants in the <i>SHANK3</i> 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. |
| first_indexed | 2024-03-11T08:46:37Z |
| format | Article |
| id | doaj.art-21baf555c4e947fa942fbdef0fffc489 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T08:46:37Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-21baf555c4e947fa942fbdef0fffc4892023-11-16T20:43:42ZengMDPI AGGenes2073-44252023-02-0114249010.3390/genes14020490Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth FactorBridgette A. Moffitt0Sara M. Sarasua1Diana Ivankovic2Linda D. Ward3Kathleen Valentine4William E. Bennett5Curtis Rogers6Katy Phelan7Luigi Boccuto8School of Nursing, Healthcare Genetics Program, Clemson University, Clemson, SC 29634, USASchool of Nursing, Healthcare Genetics Program, Clemson University, Clemson, SC 29634, USASchool of Nursing, Healthcare Genetics Program, Clemson University, Clemson, SC 29634, USASchool of Nursing, Healthcare Genetics Program, Clemson University, Clemson, SC 29634, USASchool of Nursing, Healthcare Genetics Program, Clemson University, Clemson, SC 29634, USADivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University, Riley Hospital for Children, Indianapolis, IN 46202, USAGreenwood Genetic Center, Greenwood, SC 29646, USAGenetics Laboratory, Florida Cancer Specialists & Research Institute, Fort Myers, FL 33916, USASchool of Nursing, Healthcare Genetics Program, Clemson University, Clemson, SC 29634, USAPhelan–McDermid syndrome (PMS), caused by pathogenic variants in the <i>SHANK3</i> 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.https://www.mdpi.com/2073-4425/14/2/490Phelan–McDermid syndromePMS22q13.3 deletion syndrome<i>SHANK3</i>growth hormonehGH |
| spellingShingle | Bridgette A. Moffitt Sara M. Sarasua Diana Ivankovic Linda D. Ward Kathleen Valentine William E. Bennett Curtis Rogers Katy Phelan Luigi Boccuto Stratification of a Phelan–McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor Genes Phelan–McDermid syndrome PMS 22q13.3 deletion syndrome <i>SHANK3</i> growth hormone hGH |
| 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 | Phelan–McDermid syndrome PMS 22q13.3 deletion syndrome <i>SHANK3</i> growth hormone hGH |
| url | https://www.mdpi.com/2073-4425/14/2/490 |
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