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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...

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Autores principales: 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
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
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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.
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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
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