Characterization and localization of the FMR-1 gene product associated with fragile X syndrome
Open accessAbstract
The fragile X syndrome is the most frequent form of inherited mental retardation after Down's syndrome, having an incidence of one in 1,250 males. The fragile X syndrome results from amplification of the CGG repeat found in the FMR-1 gene. This CGG repeat shows length variation in normal individuals and is increased significantly in both carriers and patients; it is located 250 base pairs distal to a CpG island which is hypermethylated in fragile X patients. The methylation probably results in downregulation of FMR-1 gene expression. No information can be deduced about the function of the FMR-1 protein from its predicted sequence. Here we investigate the nature and function of the protein encoded by the FMR-1 gene using polyclonal antibodies raised against the predicted amino-acid sequences. Four different protein products, possibly resulting from alternative splicing, have been identified by immunoblotting in lymphoblastoid cell lines of healthy individuals. All these proteins were missing in cell lines from patients not expressing FMR-1 messenger RNA. The intracellular localization of the FMR-1 gene products was investigated by transient expression in COS-1 cells and found to be cytoplasmic. Localization was also predominantly cytoplasmic in the epithelium of the oesophagus, but in some cells was obviously nuclear.
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Fragile X syndrome is a NDD where the causative gene, Fragile X Mental Retardation Protein (FMRP), is completely absent, causing a plethora of developmental abnormalities.
“Fragile X syndrome (FX) is a NDD where the causative gene, Fragile X Mental Retardation Protein (FMRP), is completely absent causing a plethora of developmental abnormalities [264, 265].”
From Development of prefrontal cortex (2022) · cites this paper as [265]
The opening passage (p. 1) links fragile X syndrome to changes in the FMR-1 gene and reports that its protein products were missing in patient cell lines lacking FMR-1 mRNA. But the paper also reports FMRP expression in a mosaic patient (p. 2), so it does not support saying the protein is completely absent in all patients. FMRP is the gene product, not the gene; the paper discusses mental retardation and syndrome manifestations, but does not establish the claimed breadth of developmental abnormalities. (LLM, conf=0.88)
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- Authors
- Verheij, C., Bakker, C. E., de Graaff, E., Keulemans, J., Willemsen, R., Verkerk, A. J. M. H., Galjaard, H., Reuser, A. J. J., Hoogeveen, A. T., & Oostra, B. A.
- Affiliations
- Erasmus University Rotterdam (NL)
- Venue
- Nature
- Published
- 1993-06
- Volume
- 363
- Issue
- 6431
- Pages
- 722-724
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1978236923
- Cited by
- 343
- References
- 18
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 9 · 2016: 8 · 2015: 14 · 2014: 10 · 2013: 13 · 2012: 9
- FWCI
- 13.46
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- fragile X syndrome, CGG repeat expansion, CpG island hypermethylation, alternative splicing, protein isoforms, gene downregulation, protein localization, cytoplasmic localization, esophageal epithelium
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cloning, Molecular, Cytoplasm, DNA, Single-Stranded, Escherichia coli, Fragile X Syndrome, Humans, Immunoenzyme Techniques, Male, Molecular Sequence Data, Mosaicism, Nerve Tissue Proteins, Precipitin Tests, Repetitive Sequences, Nucleic Acid, RNA, Messenger, Transfection, RNA-Binding Proteins, Alternative Splicing, Fragile X Messenger Ribonucleoprotein 1
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