Point mutation frequency in the FMR1 gene as revealed by fragile X syndrome screening
Abstract
Fragile X syndrome (FXS) is a common cause of intellectual disability, developmental delay and autism spectrum disorders. This syndrome is due to a functional loss of the FMR1 gene product FMRP, and, in most cases, it is caused by CGG repeat expansion in the FMR1 promoter. Yet, also other FMR1 mutations may cause a FXS-like phenotype. Since standard molecular testing does not include the analysis of the FMR1 coding region, the prevalence of point mutations causing FXS is not well known. Here, high resolution melting (HRM) was used to screen for FMR1 gene mutations in 508 males with clinical signs of mental retardation and developmental delay, but without CGG and GCC repeat expansions in the FMR1 gene and AFF2 genes, respectively. Sequence variations were identified by HRM analysis and verified by direct DNA sequencing. Two novel missense mutations (p.Gly482Ser in one patient and p.Arg534His in two unrelated patients), one intronic and two 3'-untranslated region (UTR) variations were identified in the FMR1 gene. Missense mutations in the FMR1 gene might account for a considerable proportion of cases in male patients with FXS-related symptoms, such as those linked to mental retardation and developmental delay.
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In under 1% of FXS patients, FMR1 inactivation is caused by mutations other than trinucleotide repeat expansions.
“In a small fraction (less than 1%) of patients with FXS, the inactivation of FMR1 is caused by other non-trinucleotide repeat mutations3.”
From Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome (2018) · cites this paper as [3]
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Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome
Berry-Kravis, E. M., Lindemann, L., Jønch, A. E., Apostol, G., Bear, M. F., Carpenter, R. L., Crawley, J. N., Curie, A., Des Portes, V., Hossain, F., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.221 · Cited by 336 · see citing works
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- Authors
- Handt, M., Epplen, A., Hoffjan, S., Mese, K., Epplen, J. T., & Dekomien, G.
- Affiliations
- Witten/Herdecke University (DE)
- Ruhr University Bochum (DE)
- Corresponding author
- Dekomien, Gabriele
- Venue
- Molecular and Cellular Probes
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 28
- Issue
- 5-6
- Pages
- 279-283
- ISSN
- 0890-8508 (ISSN-L)
- OpenAlex
- W1983796580
- Cited by
- 48
- References
- 59
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 2 · 2020: 7 · 2019: 5 · 2018: 3 · 2017: 8 · 2016: 4 · 2015: 1 · 2014: 2
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Probes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- fragile X syndrome, FMR1 gene, point mutations, missense mutations, FMRP, intellectual disability, developmental delay, high-resolution melting analysis, male patients
- MeSH terms
- DNA, Fragile X Syndrome, Gene Frequency, Genetic Testing, Genotype, Humans, Male, Nucleic Acid Denaturation, Phenotype, Polymerase Chain Reaction, Point Mutation, Sequence Analysis, DNA, Mutation, Missense, Polymorphism, Single Nucleotide, Fragile X Messenger Ribonucleoprotein 1, Fragile X Mental Retardation Protein
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