Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders
Mutations of the X-linked gene encoding methyl-CpG-binding protein 2 (<i>MECP2</i>) cause classical forms of Rett syndrome (RTT) in girls. A subset of patients who are recognized to have an overlapping neurological phenotype with RTT but are lacking a mutation in a gene that causes class...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/10/1437 |
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| author | Eric Frankel Avijit Podder Megan Sharifi Roshan Pillai Newell Belnap Keri Ramsey Julius Dodson Pooja Venugopal Molly Brzezinski Lorida Llaci Brittany Gerald Gabrielle Mills Meredith Sanchez-Castillo Chris D. Balak Szabolcs Szelinger Wayne M. Jepsen Ashley L. Siniard Ryan Richholt Marcus Naymik Isabelle Schrauwen David W. Craig Ignazio S. Piras Matthew J. Huentelman Nicholas J. Schork Vinodh Narayanan Sampathkumar Rangasamy |
| author_facet | Eric Frankel Avijit Podder Megan Sharifi Roshan Pillai Newell Belnap Keri Ramsey Julius Dodson Pooja Venugopal Molly Brzezinski Lorida Llaci Brittany Gerald Gabrielle Mills Meredith Sanchez-Castillo Chris D. Balak Szabolcs Szelinger Wayne M. Jepsen Ashley L. Siniard Ryan Richholt Marcus Naymik Isabelle Schrauwen David W. Craig Ignazio S. Piras Matthew J. Huentelman Nicholas J. Schork Vinodh Narayanan Sampathkumar Rangasamy |
| author_sort | Eric Frankel |
| collection | DOAJ |
| description | Mutations of the X-linked gene encoding methyl-CpG-binding protein 2 (<i>MECP2</i>) cause classical forms of Rett syndrome (RTT) in girls. A subset of patients who are recognized to have an overlapping neurological phenotype with RTT but are lacking a mutation in a gene that causes classical or atypical RTT can be described as having a ‘Rett-syndrome-like phenotype (RTT-L). Here, we report eight patients from our cohort diagnosed as having RTT-L who carry mutations in genes unrelated to RTT. We annotated the list of genes associated with RTT-L from our patient cohort, considered them in the light of peer-reviewed articles on the genetics of RTT-L, and constructed an integrated protein–protein interaction network (PPIN) consisting of 2871 interactions connecting 2192 neighboring proteins among RTT- and RTT-L-associated genes. Functional enrichment analysis of RTT and RTT-L genes identified a number of intuitive biological processes. We also identified transcription factors (TFs) whose binding sites are common across the set of RTT and RTT-L genes and appear as important regulatory motifs for them. Investigation of the most significant over-represented pathway analysis suggests that HDAC1 and CHD4 likely play a central role in the interactome between RTT and RTT-L genes. |
| first_indexed | 2024-03-11T03:50:26Z |
| format | Article |
| id | doaj.art-20acec46706042719162109c33744bd6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:50:26Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-20acec46706042719162109c33744bd62023-11-18T00:53:36ZengMDPI AGCells2073-44092023-05-011210143710.3390/cells12101437Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental DisordersEric Frankel0Avijit Podder1Megan Sharifi2Roshan Pillai3Newell Belnap4Keri Ramsey5Julius Dodson6Pooja Venugopal7Molly Brzezinski8Lorida Llaci9Brittany Gerald10Gabrielle Mills11Meredith Sanchez-Castillo12Chris D. Balak13Szabolcs Szelinger14Wayne M. Jepsen15Ashley L. Siniard16Ryan Richholt17Marcus Naymik18Isabelle Schrauwen19David W. Craig20Ignazio S. Piras21Matthew J. Huentelman22Nicholas J. Schork23Vinodh Narayanan24Sampathkumar Rangasamy25Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USAQuantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USACenter for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USACenter for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USACenter for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USADepartment of Translational Genomics, University of Southern California, Los Angeles, CA 90033, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USAQuantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USANeurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USAMutations of the X-linked gene encoding methyl-CpG-binding protein 2 (<i>MECP2</i>) cause classical forms of Rett syndrome (RTT) in girls. A subset of patients who are recognized to have an overlapping neurological phenotype with RTT but are lacking a mutation in a gene that causes classical or atypical RTT can be described as having a ‘Rett-syndrome-like phenotype (RTT-L). Here, we report eight patients from our cohort diagnosed as having RTT-L who carry mutations in genes unrelated to RTT. We annotated the list of genes associated with RTT-L from our patient cohort, considered them in the light of peer-reviewed articles on the genetics of RTT-L, and constructed an integrated protein–protein interaction network (PPIN) consisting of 2871 interactions connecting 2192 neighboring proteins among RTT- and RTT-L-associated genes. Functional enrichment analysis of RTT and RTT-L genes identified a number of intuitive biological processes. We also identified transcription factors (TFs) whose binding sites are common across the set of RTT and RTT-L genes and appear as important regulatory motifs for them. Investigation of the most significant over-represented pathway analysis suggests that HDAC1 and CHD4 likely play a central role in the interactome between RTT and RTT-L genes.https://www.mdpi.com/2073-4409/12/10/1437Rett syndromeatypical RTT syndromeRett-syndrome-like phenotypemethyl-CpG-binding protein 2neurodevelopmental disordersoverlapping phenotype |
| spellingShingle | Eric Frankel Avijit Podder Megan Sharifi Roshan Pillai Newell Belnap Keri Ramsey Julius Dodson Pooja Venugopal Molly Brzezinski Lorida Llaci Brittany Gerald Gabrielle Mills Meredith Sanchez-Castillo Chris D. Balak Szabolcs Szelinger Wayne M. Jepsen Ashley L. Siniard Ryan Richholt Marcus Naymik Isabelle Schrauwen David W. Craig Ignazio S. Piras Matthew J. Huentelman Nicholas J. Schork Vinodh Narayanan Sampathkumar Rangasamy Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders Cells Rett syndrome atypical RTT syndrome Rett-syndrome-like phenotype methyl-CpG-binding protein 2 neurodevelopmental disorders overlapping phenotype |
| title | Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders |
| title_full | Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders |
| title_fullStr | Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders |
| title_full_unstemmed | Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders |
| title_short | Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders |
| title_sort | genetic and protein network underlying the convergence of rett syndrome like rtt l phenotype in neurodevelopmental disorders |
| topic | Rett syndrome atypical RTT syndrome Rett-syndrome-like phenotype methyl-CpG-binding protein 2 neurodevelopmental disorders overlapping phenotype |
| url | https://www.mdpi.com/2073-4409/12/10/1437 |
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