Expansion of an FMR1 Grey-Zone Allele to a Full Mutation in Two Generations
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Fragile X Syndrome is caused by the expansion of an unstable CGG-repeat tract in the 5'-UTR of the FMR1 gene, which generally results in transcriptional silencing and consequent absence of the FMR1 protein. To date, the smallest premutation allele reported to expand to a full mutation allele in a single generation is 59 CGG repeats. Here, we report a single-generation expansion to a full mutation allele (male with approximately 538 CCG repeats) from a mother who is a carrier of a premutation allele of 56 CGG repeats. Furthermore, the maternal grandfather was a carrier of a gray (or intermediate)-zone allele (45 to 54 repeats) of 52 CGG repeats. Thus, in this family, a gray-zone allele expanded to the full mutation range in two generations. Interestingly, the two AGG interruptions present in the grandfather's allele were absent in the mother's premutation allele. These observations underscore the need to consider carriers of alleles of greater than 55 CGG repeats as being at risk for transmission of a full mutation allele in a single generation, and those with even smaller alleles in the gray zone as being at risk of having grandchildren with full mutation alleles.
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Expansion from a premutation to a full mutation can occur with alleles as small as 56 CGG repeats.
“Expansion from a PM to FM can occur with alleles as small as 56 CGGs (10).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [10]
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Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics
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- Authors
- Fernandez-Carvajal, I., Lopez Posadas, B., Pan, R., Raske, C., Hagerman, P. J., & Tassone, F.
- Affiliations
- University of California, Davis (US)
- University of California Davis Medical Center (US)
- Corresponding author
- Tassone, Flora
- Venue
- The Journal of Molecular Diagnostics
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 11
- Issue
- 4
- Pages
- 306-310
- ISSN
- 1525-1578 (ISSN-L)
- PMC
- PMC2710706
- OpenAlex
- W2032436286
- Cited by
- 164
- References
- 27
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2022: 1 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 9 · 2017: 7 · 2016: 18 · 2015: 4 · 2014: 15 · 2013: 14 · 2012: 12
- FWCI
- 13.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Molecular Diagnostics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD02274, P30HD002274)
- 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 › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- fragile X syndrome, FMR1 gene, CGG repeat expansion, premutation, full mutation, repeat instability, AGG interruptions, 5' untranslated region, transmission risk
- MeSH terms
- Alleles, DNA Mutational Analysis, Female, Fragile X Syndrome, Heterozygote, Humans, Male, Mutation, Pedigree, Trinucleotide Repeat Expansion, Genetic Predisposition to Disease, Fragile X Messenger Ribonucleoprotein 1
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