Cargando…
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 (MECP2) 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 RT...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217403/ https://www.ncbi.nlm.nih.gov/pubmed/37408271 http://dx.doi.org/10.3390/cells12101437 |
_version_ | 1785048529170857984 |
---|---|
author | Frankel, Eric Podder, Avijit Sharifi, Megan Pillai, Roshan Belnap, Newell Ramsey, Keri Dodson, Julius Venugopal, Pooja Brzezinski, Molly Llaci, Lorida Gerald, Brittany Mills, Gabrielle Sanchez-Castillo, Meredith Balak, Chris D. Szelinger, Szabolcs Jepsen, Wayne M. Siniard, Ashley L. Richholt, Ryan Naymik, Marcus Schrauwen, Isabelle Craig, David W. Piras, Ignazio S. Huentelman, Matthew J. Schork, Nicholas J. Narayanan, Vinodh Rangasamy, Sampathkumar |
author_facet | Frankel, Eric Podder, Avijit Sharifi, Megan Pillai, Roshan Belnap, Newell Ramsey, Keri Dodson, Julius Venugopal, Pooja Brzezinski, Molly Llaci, Lorida Gerald, Brittany Mills, Gabrielle Sanchez-Castillo, Meredith Balak, Chris D. Szelinger, Szabolcs Jepsen, Wayne M. Siniard, Ashley L. Richholt, Ryan Naymik, Marcus Schrauwen, Isabelle Craig, David W. Piras, Ignazio S. Huentelman, Matthew J. Schork, Nicholas J. Narayanan, Vinodh Rangasamy, Sampathkumar |
author_sort | Frankel, Eric |
collection | PubMed |
description | Mutations of the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2) 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. |
format | Online Article Text |
id | pubmed-10217403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102174032023-05-27 Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders Frankel, Eric Podder, Avijit Sharifi, Megan Pillai, Roshan Belnap, Newell Ramsey, Keri Dodson, Julius Venugopal, Pooja Brzezinski, Molly Llaci, Lorida Gerald, Brittany Mills, Gabrielle Sanchez-Castillo, Meredith Balak, Chris D. Szelinger, Szabolcs Jepsen, Wayne M. Siniard, Ashley L. Richholt, Ryan Naymik, Marcus Schrauwen, Isabelle Craig, David W. Piras, Ignazio S. Huentelman, Matthew J. Schork, Nicholas J. Narayanan, Vinodh Rangasamy, Sampathkumar Cells Article Mutations of the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2) 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. MDPI 2023-05-21 /pmc/articles/PMC10217403/ /pubmed/37408271 http://dx.doi.org/10.3390/cells12101437 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 Frankel, Eric Podder, Avijit Sharifi, Megan Pillai, Roshan Belnap, Newell Ramsey, Keri Dodson, Julius Venugopal, Pooja Brzezinski, Molly Llaci, Lorida Gerald, Brittany Mills, Gabrielle Sanchez-Castillo, Meredith Balak, Chris D. Szelinger, Szabolcs Jepsen, Wayne M. Siniard, Ashley L. Richholt, Ryan Naymik, Marcus Schrauwen, Isabelle Craig, David W. Piras, Ignazio S. Huentelman, Matthew J. Schork, Nicholas J. Narayanan, Vinodh Rangasamy, Sampathkumar Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217403/ https://www.ncbi.nlm.nih.gov/pubmed/37408271 http://dx.doi.org/10.3390/cells12101437 |
work_keys_str_mv | AT frankeleric geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT podderavijit geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT sharifimegan geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT pillairoshan geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT belnapnewell geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT ramseykeri geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT dodsonjulius geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT venugopalpooja geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT brzezinskimolly geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT llacilorida geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT geraldbrittany geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT millsgabrielle geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT sanchezcastillomeredith geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT balakchrisd geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT szelingerszabolcs geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT jepsenwaynem geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT siniardashleyl geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT richholtryan geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT naymikmarcus geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT schrauwenisabelle geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT craigdavidw geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT pirasignazios geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT huentelmanmatthewj geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT schorknicholasj geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT narayananvinodh geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders AT rangasamysampathkumar geneticandproteinnetworkunderlyingtheconvergenceofrettsyndromelikerttlphenotypeinneurodevelopmentaldisorders |