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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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Detalles Bibliográficos
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
Descripción
Sumario: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.