Clinical and molecular characteristics of FMR1 microdeletion in patient with fragile X syndrome and review of the literature
CONCLUSION: According to review of previous cases with FMR1 microdeletions, most patients carrying concurrent deletion and full mutation had typical clinical features of FXS. To our knowledge, our case is the first to describe mosaicism of a premutation and microdeletion in the FMR1 gene. The patient was probably protected from the effects of the deletion by mosaicism with premutation allele, leading to milder phenotype. It is thus important to consider appropriate techniques for detecting FMR1 variants other than repeat expansions which cannot be detected by routine FXS diagnosis.PMID:38142803 | DOI:10.1016/j.cca.2023.117...
Source: International Journal of Clinical Chemistry - December 24, 2023 Category: Chemistry Authors: Areerat Hnoonual Oradawan Plong-On Juthamas Worachotekamjorn Chariyawan Charalsawadi Pornprot Limprasert Source Type: research
GSE218680 Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome
Series Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensThis SuperSeries is composed of the SubSeries listed below. (Source: GEO: Gene Expression Omnibus)
Source: GEO: Gene Expression Omnibus - December 21, 2023 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Other Homo sapiens Source Type: research
GSE218679 Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome [Nanopore]
Contributors : Thomas Malachowski ; Keerthivasan R Chandradoss ; Linda Zhou ; Ravi Boya ; Ashley Cook ; Jennifer E Phillips-CreminsSeries Type : OtherOrganism : Homo sapiensShort tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find Megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X-chromosome in induced pluripotent stem cell (iPSC)-derived neural progenitors, B-cells, and fibroblasts with mutation-length CGG expansion....
Source: GEO: Gene Expression Omnibus - December 21, 2023 Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research
GSE218678 Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome [WGS]
Contributors : Thomas Malachowski ; Keerthivasan R Chandradoss ; Linda Zhou ; Ravi Boya ; Ashley Cook ; Jennifer E Phillips-CreminsSeries Type : OtherOrganism : Homo sapiensShort tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find Megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X-chromosome in induced pluripotent stem cell (iPSC)-derived neural progenitors, B-cells, and fibroblasts with mutation-length CGG expansion....
Source: GEO: Gene Expression Omnibus - December 21, 2023 Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research
GSE218677 Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome [CUT & RUN]
Contributors : Thomas Malachowski ; Keerthivasan R Chandradoss ; Linda Zhou ; Ravi Boya ; Ashley Cook ; Jennifer E Phillips-CreminsSeries Type : OtherOrganism : Homo sapiensShort tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find Megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X-chromosome in induced pluripotent stem cell (iPSC)-derived neural progenitors, B-cells, and fibroblasts with mutation-length CGG expansion....
Source: GEO: Gene Expression Omnibus - December 21, 2023 Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research
GSE218676 Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome [RNA-seq]
Contributors : Thomas Malachowski ; Keerthivasan R Chandradoss ; Linda Zhou ; Ravi Boya ; Ashley Cook ; Jennifer E Phillips-CreminsSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensShort tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find Megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X-chromosome in induced pluripotent stem cell (iPSC)-derived neural progenitors, B-cells, and fi...
Source: GEO: Gene Expression Omnibus - December 21, 2023 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
GSE218675 Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome [Hi-C]
Contributors : Thomas Malachowski ; Keerthivasan R Chandradoss ; Linda Zhou ; Ravi Boya ; Ashley Cook ; Jennifer E Phillips-CreminsSeries Type : OtherOrganism : Homo sapiensShort tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find Megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X-chromosome in induced pluripotent stem cell (iPSC)-derived neural progenitors, B-cells, and fibroblasts with mutation-length CGG expansion....
Source: GEO: Gene Expression Omnibus - December 21, 2023 Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research
GSE218674 Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome [ChIP-seq]
Contributors : Thomas Malachowski ; Keerthivasan R Chandradoss ; Linda Zhou ; Ravi Boya ; Ashley Cook ; Jennifer E Phillips-CreminsSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensShort tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find Megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X-chromosome in induced pluripotent stem cell (iPSC)-derived neural progenitors, B...
Source: GEO: Gene Expression Omnibus - December 21, 2023 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Expert commentary for fragile X premutation mimicking late onset hereditary spastic paraplegia
Fraiman et al. describe a case of a late-onset spastic ataxia, which raises important points regarding the often-challenging genetic diagnosis of this group of disorders. The individual demonstrated gait and upper limb ataxia, as well features consistent with spastic paraparesis in the lower limbs. Key diagnostic clues included a family history of fragile X syndrome in two nephews, in addition to characteristic MRI brain findings of T2/FLAIR hyperintensities in bilateral middle cerebellar peduncles (MCPs). (Source: Parkinsonism and Related Disorders)
Source: Parkinsonism and Related Disorders - December 20, 2023 Category: Neurology Authors: Laura Ivete Rudaks, Dennis Yeow, Kishore Raj Kumar Source Type: research
Genes, Vol. 15, Pages 6: PGT-M for Premature Ovarian Failure Related to CGG Repeat Expansion of the FMR1 Gene
orrentino
Primary ovarian failure (POF) is caused by follicle exhaustion and is associated with menstrual irregularities and elevated gonadotropin levels, which lead to infertility before the age of 40 years. The etiology of POI is mostly unknown, but a heterogeneous genetic and familial background can be identified in a subset of cases. Abnormalities in the fragile X mental retardation 1 gene (FMR1) are among the most prevalent monogenic causes of POI. These abnormalities are caused by the expansion of an unstable CGG repeat in the 5′ untranslated region of FMR1. Expansions over 200 repeats cause fragile...
Source: Genes - December 19, 2023 Category: Genetics & Stem Cells Authors: Tiziana Persico Maria Lucrezia Tranquillo Renato Seracchioli Daniela Zuccarello Ugo Sorrentino Tags: Review Source Type: research
Development of small-molecule inhibitors that target PI3K β
Drug Discov Today. 2023 Dec 7:103854. doi: 10.1016/j.drudis.2023.103854. Online ahead of print.ABSTRACTPhosphatidylinositol-3 kinase (PI3K) β, a subtype of class I PI3Ks, has an essential role in PTEN-deficient tumors and links to thrombosis, male fertility, and Fragile X syndrome. PI3Kβ-specific targeting therapy could be an efficacious treatment for diseases highly dependent on PI3Kβ, while mitigating the severe toxicity of pan-PI3K inhibitors. Achieving selectivity can be accomplished through three primary strategies, namely, binding to the induced lipophilic pocket, targeting the unique amino acid residue of PI3Kβ,...
Source: Drug Discovery Today - December 9, 2023 Category: Drugs & Pharmacology Authors: Yanzhen Yu Dongyan Gu Lvtao Cai Haodong Yang Rong Sheng Source Type: research
Development of small-molecule inhibitors that target PI3K β
Drug Discov Today. 2023 Dec 7:103854. doi: 10.1016/j.drudis.2023.103854. Online ahead of print.ABSTRACTPhosphatidylinositol-3 kinase (PI3K) β, a subtype of class I PI3Ks, has an essential role in PTEN-deficient tumors and links to thrombosis, male fertility, and Fragile X syndrome. PI3Kβ-specific targeting therapy could be an efficacious treatment for diseases highly dependent on PI3Kβ, while mitigating the severe toxicity of pan-PI3K inhibitors. Achieving selectivity can be accomplished through three primary strategies, namely, binding to the induced lipophilic pocket, targeting the unique amino acid residue of PI3Kβ,...
Source: Drug Discovery Today - December 9, 2023 Category: Drugs & Pharmacology Authors: Yanzhen Yu Dongyan Gu Lvtao Cai Haodong Yang Rong Sheng Source Type: research
Development of small-molecule inhibitors that target PI3K β
Drug Discov Today. 2023 Dec 7:103854. doi: 10.1016/j.drudis.2023.103854. Online ahead of print.ABSTRACTPhosphatidylinositol-3 kinase (PI3K) β, a subtype of class I PI3Ks, has an essential role in PTEN-deficient tumors and links to thrombosis, male fertility, and Fragile X syndrome. PI3Kβ-specific targeting therapy could be an efficacious treatment for diseases highly dependent on PI3Kβ, while mitigating the severe toxicity of pan-PI3K inhibitors. Achieving selectivity can be accomplished through three primary strategies, namely, binding to the induced lipophilic pocket, targeting the unique amino acid residue of PI3Kβ,...
Source: Drug Discovery Today - December 9, 2023 Category: Drugs & Pharmacology Authors: Yanzhen Yu Dongyan Gu Lvtao Cai Haodong Yang Rong Sheng Source Type: research
Structural peculiarities of tandem repeats and their clinical significance
In this study, we employed our novel algorithm grounded in finite automata theory, which we refer to as Dafna, to investigate for the first time the likelihood of these nucleotide sequences forming non-canonical DNA structures (NS). Such structures include G-quadruplexes, i-motifs, hairpins, and triplexes. The tandem repeats under consideration in our research encompassed sequences containing 1 to 6 nucleotides per repeated fragment. For comparison, we employed a set of randomly generated sequences of the same length (60 nucleotides) as a benchmark. The outcomes of our research exposed a disparity between the potential for...
Source: Biochemical and Biophysical Research communications - December 6, 2023 Category: Biochemistry Authors: Stanislav S Bachurin Mikhail V Yurushkin Ilya A Slynko Mikhail E Kletskii Oleg N Burov Dmitriy P Berezovskiy Source Type: research
Transcranial direct current stimulation combined with speech therapy in Fragile X syndrome patients: a pilot study
ConclusionOur study provides novel evidence that left anodal prefrontal tDCS combined with standard speech therapy could be effective in enhancing language function in FXS patients, mainly by inducing a rebalance of the dysfunctional prefrontal cortical excitability. (Source: Frontiers in Neurology)
Source: Frontiers in Neurology - December 5, 2023 Category: Neurology Source Type: research
