The emerging fragile X premutation phenotype: Evidence from the domain of social cognition
Abstract
Fragile X syndrome is a neurodevelopmental disorder that is caused by large methylated expansions of a CGG repeat (>200) region upstream of the FMR1 gene that results in the lack of expression of the fragile X mental retardation protein (FMRP). Affected individuals display a neurobehavioral phenotype that includes a significant impairment in social cognition alongside deficits in attentional control, inhibition and working memory. In contrast, relatively little is known about the trajectory and specificity of any cognitive impairment associated with the fragile X premutation ("carrier-status") (approximately 55-200 repeats). Here, we focus on one aspect of cognition that has been well documented in the fragile X full mutation, namely social cognition. The results suggest that premutation males display a pattern of deficit similar in profile, albeit milder in presentation, to that of the full mutation. However, little evidence emerged for a correlation between CGG repeat length and severity of phenotypic outcomes. The findings are discussed in the context of functional neuroimaging and brain-behaviour-molecular correlates. We speculate that the deficiencies in social cognition are attributable to impairment of neural pathways modulated by the cerebellum.
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In premutation carriers, shyness, anxiety, social deficits, and ADHD are common, particularly in boys.
“In PM carriers, shyness, anxiety, social deficits, and ADHD are some of the most common features observed, particularly in boys (29)(30)(31).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [29]
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- Authors
- Cornish, K., Kogan, C., Turk, J., Manly, T., James, N., Mills, A., & Dalton, A.
- Affiliations
- McGill University (CA)
- MRC Cognition and Brain Sciences Unit (GB)
- University of Nottingham (GB)
- University of London (GB)
- University of Cambridge (GB)
- Corresponding author
- Cornish, Kim
- Venue
- Brain and Cognition
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 57
- Issue
- 1
- Pages
- 53-60
- ISSN
- 0278-2626 (ISSN-L)
- OpenAlex
- W2148890222
- Cited by
- 148
- References
- 49
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 11 · 2015: 5 · 2014: 10 · 2013: 8 · 2012: 13
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain and Cognition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- fragile X premutation, fragile X syndrome, social cognition, FMRP, CGG repeat expansion, FMR1 gene, premutation carriers, cerebellum, cognitive impairment, neurodevelopmental disorders, functional neuroimaging
- MeSH terms
- Adolescent, Adult, Aged, Alleles, Cognition, Cognition Disorders, DNA, Emotions, Fragile X Syndrome, Heterozygote, Humans, Imagination, Intelligence, Male, Middle Aged, Mutation, Nerve Tissue Proteins, Phenotype, Repetitive Sequences, Nucleic Acid, Severity of Illness Index, Social Perception, Matched-Pair Analysis, RNA-Binding Proteins, Recognition, Psychology, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1
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