{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Barna Fodor"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000512"],"host":["EGA"],"description":["EGA DAC EGAC00001000512"],"repository":["EGA"],"email":["barna.fodor@novartis.com"],"pubmed_abstract":["In fragile X syndrome (FXS), CGG repeat expansion greater than 200 triplets is believed to trigger FMR1 gene silencing and disease etiology. However, FXS siblings have been identified with more than 200 CGGs, termed unmethylated full mutation (UFM) carriers, without gene silencing and disease symptoms. Here, we show that hypomethylation of the FMR1 promoter is maintained in induced pluripotent stem cells (iPSCs) derived from two UFM individuals. However, a subset of iPSC clones with large CGG expansions carries silenced FMR1. Furthermore, we demonstrate de novo silencing upon expansion of the CGG repeat size. FMR1 does not undergo silencing during neuronal differentiation of UFM iPSCs, and expression of large unmethylated CGG repeats has phenotypic consequences resulting in neurodegenerative features. Our data suggest that UFM individuals do not lack the cell-intrinsic ability to silence FMR1 and that inter-individual variability in the CGG repeat size required for silencing exists in the FXS population."],"pubmed_title":["CGG Repeat-Induced FMR1 Silencing Depends on the Expansion Size in Human iPSCs and Neurons Carrying Unmethylated Full Mutations."],"pubmed_authors":["Brykczynska Urszula U, Pecho-Vrieseling Eline E, Thiemeyer Anke A, Klein Jessica J, Fruh Isabelle I, Doll Thierry T, Manneville Carole C, Fuchs Sascha S, Iazeolla Mariavittoria M, Beibel Martin M, Roma Guglielmo G, Naumann Ulrike U, Kelley Nicholas N, Oakeley Edward J EJ, Mueller Matthias M, Gomez-Mancilla Baltazar B, Bühler Marc M, Tabolacci Elisabetta E, Chiurazzi Pietro P, Neri Giovanni G, Bouwmeester Tewis T, Di Giorgio Francesco Paolo FP, Fodor Barna D BD"],"pubmed_title_synonyms":["dfxr1, FMR1, human being, dmfr1, dfmr, fmr, dFMRP, Modern, Nerve, cg6203, BcDNA:GM08679, Cell, FRAXA, Human, POF, dFMR1, dFmr1, dFMR, Homo sapiens, Mutations., Carrying, fmr1, Man, fmr-1, DmelCG6203, FXR, Fmr-1, Fmrp, FMRp, Nerve Cells, Man (Taxonomy), POF1, EP(3)3517, dfxr, dFXRP, dfmr1, human, FMRP, AT24755, FMR, dFmrp, Modern Man, Cells, dFXR, Neuron, CG6203, fmrp, dFXR1, Nerve Cell"],"pubmed_abstract_synonyms":["dmfr1, FRAXA Syndromes, dFMRP, acetylglucosaminyltransferase-like protein, IPS, mental retardation, Mbp1, Fibroblast Derived IPS Cells, hiPSC, BcDNA:GM08679, Mutations, FRAX, dmTAF[[II]]230, School-Age, POF, dFMR1, dFmr1, diseases, Fragile X Syndromes, symptoms, pathogenesis, diseases and disorders, iPS cell, myd, Fibroblast-Derived IPS Cells, human disease, like-acetylglucosaminyltransferase, TFIID TAF250, cel, EP(3)3517, inhibition of gene expression, Mbp-1, FRAXA Syndrome, FMR, dFmrp, X Linked Mental Retardation and Macroorchidism, Homo sapiens disease, CG6203, Marker X, screening, dTAF[[II]]230, primary ovarian insufficiency, fmr, gyltl1b-b, TAF200, Brother, cg6203, FRAXE Syndromes, TAFII-250, Martin-Bell Syndrome, TAF250/230, marker 10 syndrome, FRAXA, X-linked mental retardation and macroorchidism, FRAXE, TAFII250, gene silencing, MDDGA6, School Age, mKIAA0609, Diseases, X-Linked Mental Retardation and Macroorchidism, KIAA0609, acetylglucosaminyltransferase-like 1A, fmr-1, DmelCG6203, fg, Populations, X-Linked, gyltl1b, Martin-Bell, POF1, Fibroblast-Derived IPS, mdc1d, dfxr, signs, fragile 10 intellectual disability syndrome, Marker X Syndromes, Fibroblast-Derived, CG17603, dfmr1, LARGE_HUMAN, TAF[[II]], associated with Marxq28, FRAXE Syndrome, disease, MDC1D, fragile 10 premature ovarian failure, fra(X) syndrome, Syndromes, enr, X-linked intellectual disability and macroorchidism, Taf250, SR3-5, Cells, Fibroblast-Derived Induced Pluripotent Stem Cells, dFXR, Sisters, School-Age Population, fragile 10 mental retardation syndrome, TAF230, other disease, dfxr1, epigenetic, d230, FMR1, X-linked, Fibroblast-Derived IPS Cell, Induced Pluripotent Stem Cell, Gene, dTAFII250, EfW1, IPS Cells, LARGE1, froggy, Gyltl1a, Fragile X tremor/ataxia syndrome, dmTAF1, Taf230, Mar (X) Syndrome, disease or disorder, fmr1, intellectual disability, TAF250, Fmr-1, Brothers, School-Age Populations, Fmrp, Taf200, FMRp, Associated With Marxq28, Mental Retardation, dTAF[[II]]250, cell, MDDGB6, Gene Inactivation, Taf1p, dFXRP, LARGE, causes, Population, Fra(X) Syndrome, Human Induced Pluripotent Stem Cells, non-neoplastic, BPFD#36, dTAF250, FMRP, Syndrome, causality, disorder, fmrp, dFXR1, School Age Population, TAF, Fragile X Mental Retardation Syndrome, Fragile X, TAF[[II]]250, findings, dfmr, Inactivation, disorders, l(3)84Ab, medical condition, BG:DS00004.13, Cell, dTAF230, Triplet, iPSC, dFMR, Fibroblast Derived Induced Pluripotent Stem Cells, Marker X Syndrome, p230, Associated With Fragile Site Fraxe, TAF[[II]]250/230, condition, TFIID, fragile 10 syndrome, IPS Cell, Silencing, INSDC_feature:regulatory, fragile X-associated, FXS, FXR, Taf[[II]]250, School Age Populations., Fragile X-F Mental Retardation Syndrome, TAF[[II]]230, Martin Bell Syndrome, Sibling, TAF[II]250, Sister, DmelCG17603, AT24755, like-glycosyltransferase, Human Induced Pluripotent Stem Cell, glycosyltransferase-like protein LARGE1, Intrinsic, TAF1"],"additional_accession":[]},"is_claimable":false,"name":"Novartis-Cattolica UFM collaboration Data Access Committee","description":"Data Access Committee EGAC00001000512","dates":{"output":"2025-1-9"},"accession":"EGAC00001000512","cross_references":{"TAXONOMY":["9606"],"pubmed":["27840045"],"EGA":["EGAS00001001737","EGAD00001002276"]}}