RESUMEN
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.
Asunto(s)
Trastornos del Neurodesarrollo , Síndrome de Rett , Humanos , Síndrome de Rett/genética , Proteína 2 de Unión a Metil-CpG/genética , Mutación/genética , Fenotipo , Factores de Transcripción/genéticaRESUMEN
Selenoproteins are important for normal brain function, and decreased function of selenoproteins can lead to impaired cognitive function and neurological disorders. This review examines the possible roles of selenoproteins in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and epilepsy. Selenium deficiency is associated with cognitive decline, and selenoproteins may be helpful in preventing neurodegeneration in AD. PD is associated with impaired function of glutathione peroxidase selenoenzymes. In HD, selenium deters lipid peroxidation by increasing specific glutathione peroxidases. Selenium deficiency increases risk of seizures in epilepsy, whereas supplementation may help to alleviate seizures. Further studies on the mechanisms of selenoprotein function will increase our understanding of how selenium and selenoproteins can be used in treatment and prevention of brain disorders.