SynthesisEuropean journal of human genetics : EJHG2017
Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome.
Synthesis in European journal of human genetics : EJHG, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Safety and Tolerability of CTH120, First-in-human Phase I Study Encompassing Three Parts: Single and Multiple Ascending Doses and Potential Food Interaction
Assessment of Neural Biomarkers in Adult Subjects With Fragile X Syndrome and Typically Developing Subjects
Evaluation of the Safety, Tolerability, and Effectiveness of CTH120 in Adult Males With Fragile X Syndrome
Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- Targeted long-read genomic and epigenomic profiling enhances timely comprehensive variant discovery in hypotonia and muscle weakness.BMC medicine · 2026Article
- Fragile X-associated tremor/ataxia syndrome: a case report with atypical spinal cord atrophy and altered somatosensory evoked potentials.Journal of neurology · 2025Article
- Behavioral screening reveals a conserved residue in Y-Box RNA-binding protein required for associative learning and memory in C. elegans.PLoS genetics · 2024Article
- Behavioral screening of conserved RNA-binding proteins reveals CEY-1/YBX RNA-binding protein dysfunction leads to impairments in memory and cognition.bioRxiv : the preprint server for biology · 2024Article
- Phenotypic variability to medication management: an update on fragile X syndrome.Human genomics · 2023Review
- Native functions of short tandem repeats.eLife · 2023Article
- Executive Function and Working Memory Deficits in Females with Fragile X Premutation.Life (Basel, Switzerland) · 2023Article
- Case report: genetic analysis of a novel frameshift mutation in FMR1 gene in a Chinese family.Frontiers in genetics · 2023Article
- Folding Mechanism and Aggregation Propensity of the KH0 Domain of FMRP and Its R138Q Pathological Variant.International journal of molecular sciences · 2022Article
- Clinical significance of matrix metalloproteinase-9 in Fragile X Syndrome.Scientific reports · 2022Article
- Review
- Article
- GC-rich repeat expansions: associated disorders and mechanisms.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2021Article
- Beyond Trinucleotide Repeat Expansion in Fragile X Syndrome: Rare Coding and Noncoding Variants inGenes · 2021Article
- Article
- RNA-binding proteins in neurological development and disease.RNA biology · 2021Review
- Clinical Characteristics of Fragile X Syndrome Patients in Japan.Yonago acta medica · 2021Article
- Characterization ofFrontiers in genetics · 2021Article
- FMRP-Driven Neuropathology in Autistic Spectrum Disorder and Alzheimer's disease: A Losing Game.Frontiers in molecular biosciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fragile-X syndrome (FXS) is a frequent genetic form of intellectual disability (ID). The main recurrent mutagenic mechanism causing FXS is the expansion of a CGG repeat sequence in the 5'-UTR of the FMR1 gene, therefore, routinely tested in ID patients. We report here three FMR1 intragenic pathogenic variants not affecting this sequence, identified using high-throughput sequencing (HTS): a previously reported hemizygous deletion encompassing the last exon of FMR1, too small to be detected by array-CGH and inducing decreased expression of a truncated form of FMRP protein, in three brothers with ID (family 1) and two splice variants in boys with sporadic ID: a de novo variant c.990+1G>A (family 2) and a maternally inherited c.420-8A>G variant (family 3). After clinical reevaluation, the five patients presented features consistent with FXS (mean Hagerman's scores=15). We conducted a systematic review of all rare non-synonymous variants previously reported in FMR1 in ID patients and showed that six of them are convincing pathogenic variants. This study suggests that intragenic FMR1 variants, although much less frequent than CGG expansions, are a significant mutational mechanism leading to FXS and demonstrates the interest of HTS approaches to detect them in ID patients with a negative standard work-up.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.