Elevated FMR1-mRNA and lowered FMRP - A double-hit mechanism for psychiatric features in men with FMR1 premutations.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
23 06 2020
23 06 2020
Historique:
received:
19
09
2016
accepted:
22
05
2020
revised:
19
05
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
22
6
2021
Statut:
epublish
Résumé
Fragile X syndrome (FXS) is caused by a full mutation of the FMR1 gene (>200 CGG repeats and subsequent methylation), such that there is little or no FMR1 protein (FMRP) produced, leading to intellectual disability (ID). Individuals with the premutation allele (55-200 CGG repeats, generally unmethylated) have elevated FMR1 mRNA levels, a consequence of enhanced transcription, resulting in neuronal toxicity and a spectrum of premutation-associated disorders, including the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Here we described 14 patients who had both lowered FMRP and elevated FMR1 mRNA levels, representing dual mechanisms of clinical involvement, which may combine features of both FXS and FXTAS. In addition, the majority of these cases show psychiatric symptoms, including bipolar disorder, and/or psychotic features, which are rarely seen in those with just FXS.
Identifiants
pubmed: 32576818
doi: 10.1038/s41398-020-00863-w
pii: 10.1038/s41398-020-00863-w
pmc: PMC7311546
doi:
Substances chimiques
FMR1 protein, human
0
RNA, Messenger
0
Fragile X Mental Retardation Protein
139135-51-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
205Subventions
Organisme : NICHD NIH HHS
ID : P30 HD002274
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD079125
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD040661
Pays : United States
Organisme : NCBDD CDC HHS
ID : U50 DD000596
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103526
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000002
Pays : United States
Organisme : U.S. Department of Health & Human Services | Health Resources and Services Administration (Health Resources & Services Administration)
ID : 90DD0596
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | NICHD | National Center for Medical Rehabilitation Research (NCMRR)
ID : HD036072
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ID : HD040661
Pays : International
Organisme : NICHD NIH HHS
ID : R01 HD036071
Pays : United States
Organisme : DH | NIHR | Research Trainees Coordinating Centre (NIHR Research Trainees Coordinating Centre)
ID : U54HD079125
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ID : HD036071
Pays : International
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