04529nam 2201201z- 450 991036775910332120231214133151.03-03921-506-X(CKB)4100000010106126(oapen)https://directory.doabooks.org/handle/20.500.12854/61057(EXLCZ)99410000001010612620202102d2019 |y 0engurmn|---annantxtrdacontentcrdamediacrrdacarrierTowards Mechanism-based Treatments for Fragile X SyndromeMDPI - Multidisciplinary Digital Publishing Institute20191 electronic resource (250 p.)3-03921-505-1 It has been more than 25 years since the identification of the FMR1 gene and the demonstration of the causative role of CGG-repeat expansion in the disease pathology of fragile X syndrome (FXS), but the underlying mechanisms involved in the expansion mutation and the resulting gene silencing still remain elusive. Our understanding of the pathways impacted by the loss of FMRP function has grown tremendously, and has opened new avenues for targeted treatments for FXS. However, the failure of recent clinical trials that were based on successful preclinical studies using the Fmr1 knockout mouse model has forced the scientific community to revisit clinical trial design and identify objective outcome measures. There has also been a renewed interest in restoring FMR1 gene expression as a possible treatment approach for FXS. This special issue of Brain Sciences highlights the progress that has been made towards understanding the disease mechanisms and how this has informed the development of treatment strategies that are being explored for FXS.lymphoblastpluripotent stem cellsFMR1Gene editingX chromosomeFmr1epigenetic gene silencingFMR1 geneFragile X syndrome 1repeat instabilitycharacteristics that have the greatest impactDNA instabilityworking memorylanguage developmentmosaicismCRISPR 3clinical trialsautism spectrum disordersFmr1 KO mouseautomated vocal analysisbase excision repair (BER)inhibitory controlcerebral spinal fluidiPSCdrug developmenttargeted treatmentsmolecular biomarkersviral vectoravoidancebiomarkerset-shiftingearly identificationexpansionanxietyplanningvoice of the personmismatch repair (MMR)gene reactivationdouble-strand break repair (DSBR)newborn screeningintellectual disabilityprocessing speedvoice of the patientfragile X syndromeadeno-associated virusneurodevelopmental disordershistone methylationNon-homologous end-joining (NHEJ)ASDFxr2Fragile X-associated Tremor/Ataxia Syndrome 2Trinucleotide Repeat 4CGG Repeat Expansion DiseaseDNA methylationcontractionfragile X mental retardation proteinRNA:DNA hybridbehaviordevelopmental disorderscognitionfemalesFMRPFragile X Syndromeunstable repeat diseasesprotein synthesisbraincognitive flexibilitytreatment developmentfibroblastPRC2transcription coupled repair (TCR)best practicesattentionFragile Xexecutive functionKumari Damanauth1311272Gazy InbalauthBOOK9910367759103321Towards Mechanism-based Treatments for Fragile X Syndrome3030079UNINA