Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders.

Autor: Frankel E; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Podder A; Quantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Sharifi M; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Pillai R; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Belnap N; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA.; Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Ramsey K; Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Dodson J; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Venugopal P; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Brzezinski M; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Llaci L; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA.; Quantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Gerald B; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Mills G; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Sanchez-Castillo M; Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Balak CD; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Szelinger S; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Jepsen WM; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Siniard AL; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Richholt R; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Naymik M; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Schrauwen I; Center for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USA., Craig DW; Department of Translational Genomics, University of Southern California, Los Angeles, CA 90033, USA., Piras IS; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Huentelman MJ; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA.; Quantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Schork NJ; Quantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA.; City of Hope National Medical Center, Duarte, CA 91010, USA., Narayanan V; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA.; Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA., Rangasamy S; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA.; Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA.
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 May 21; Vol. 12 (10). Date of Electronic Publication: 2023 May 21.
DOI: 10.3390/cells12101437
Abstrakt: 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.
Databáze: MEDLINE
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