Phenotypic Involvement in Females With the FMR1 Gene Mutation

Riddle, Jeannette E.; Cheema, Amrita K.; Sobesky, William E.; Gardner, Sid; Taylor, Annette K.; Pennington, Bruce F.; Hagerman, Randi J.

doi:10.1352/0895-8017(1998)102<0590:piifwt>2.0.co;2

Cited by 115 publications

(74 citation statements)

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“…Structural neuroimaging studies have shown specific volumetric differences between normal controls and females with fraX in the hippocampus, cerebellar vermis, fourth ventricle, caudate nucleus, lateral ventricles, and thalamus (5)(6)(7)(8)(9). fraX in females is associated with a well characterized neurocognitive and neurobehavioral profile of deficits in executive functioning (10), visuospatial processing (11,12), and mathematical reasoning (13). These and other problems significantly disrupt academic, vocational, and social functioning in females with fraX.…”

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confidence: 99%

Frontostriatal deficits in fragile X syndrome: Relation to FMR1 gene expression

Menon

Leroux

White

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

127

105

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Fragile X syndrome (fraX) is the most common known cause of inherited developmental disability. fraX is associated with a CGG expansion in the FMR1 gene on the long arm of the X chromosome. Behavioral deficits, including problems with impulse control and distractibility, are common in fraX. We used functional brain imaging with a Go͞NoGo task to examine the neural substrates of response inhibition in females with fraX (ages 10 -22) and age-and gendermatched typically developing subjects. Although subjects with fraX had significantly lower IQ scores, as a group their performance on the Go͞NoGo task was equivalent to that of the typically developing group. However, females with fraX showed abnormal activation patterns in several cortical and subcortical regions, with significantly reduced activation in the supplementary motor area, anterior cingulate and midcingulate cortex, basal ganglia, and hippocampus. An important finding of our study is that neural responses in the right ventrolateral prefrontal cortex (PFC) and the left and right striatum were correlated with the level of FMR1 gene expression. Our findings support the hypothesis that frontostriatal regions typically associated with response inhibition are dysfunctional in females with fraX. In addition to task-related activation deficits, reduced levels of ''deactivation'' were observed in the ventromedial PFC, and, furthermore, these reductions were correlated with the level of FMR1 gene expression. The ventromedial PFC is a key node in a ''default mode'' network that monitors mental and physiological states; we suggest that self-monitoring processes may be aberrant in fraX.genetic ͉ Go͞NoGo ͉ response inhibition ͉ prefrontal cortex ͉ basal ganglia T he effect of genetic factors on human brain function is a topic of increasing interest within the field of cognitive neuroscience. In particular, the study of individuals with homogeneous genetic abnormalities and neurocognitive dysfunction can potentially serve as a prototype for advancing our knowledge of specific associations among genetic, neurobiological, and behavioral variables (1, 2). In this study, we used functional MRI (fMRI) to study deficits in executive function among females with fragile X syndrome (fraX).fraX occurs in 1 of every 2,000-5,000 live births and is the most common known cause of inherited developmental disability. fraX affects both males and females. However, because the mutation occurs in an X chromosome gene, males are more uniformly and severely affected as opposed to females, who show a considerably wider spectrum of severity. Thus we chose to study females to more accurately elucidate the spectrum of neurobiological effects associated with fraX and reduced fragile X mental retardation protein (FMRP). In individuals with fraX, the cytogenetic fragile site on the long arm of the X chromosome, from which the syndrome derives its name, is typically caused by a mutation in which Ͼ200 (up to 2,000) cytosineguanine-guanine (CGG) triplet repeats occur within the promoter region of the ...

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mentioning

confidence: 99%

Frontostriatal deficits in fragile X syndrome: Relation to FMR1 gene expression

Menon

Leroux

White

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

127

105

View full text Add to dashboard Cite

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“…Even though, and contrary to expectation, there are reported several subgroups of male and female premutation carriers displaying features consistent with the typical clinical spectrum of FXS. For instance, Riddle andco-workers (1998) andHagerman (2002) described a group of premutation carriers with prominent ears and joint laxity; or with learning disabilities, attention deficit/hyperactivity disorder (ADHD), or difficulty with math (Riddle et al, 1998, reviewed in Hagerman & Hagerman 2004). In addition, some carriers have emotional problems, including anxiety, obsessional thinking, schizotypy, and/or depression Rodriguez-Revenga et al, 2008a).…”

Section: Fragile X Syndrome Premutation and Fxtas Identificationmentioning

confidence: 99%

Neuroimaging - Clinical Applications

Bright¹

2012

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“…Even though, and contrary to expectation, there are reported several subgroups of male and female premutation carriers displaying features consistent with the typical clinical spectrum of FXS. For instance, Riddle and co-workers (1998) and Hagerman (2002) described a group of premutation carriers with prominent ears and joint laxity; or with learning disabilities, attention deficit/hyperactivity disorder (ADHD), or difficulty with math (Riddle et al, 1998, reviewed in Hagerman & Hagerman 2004). In addition, some carriers have emotional problems, including anxiety, obsessional thinking, schizotypy, and/or depression Rodriguez-Revenga et al, 2008a).…”

Section: Fragile X Syndrome Premutation and Fxtas Identificationmentioning

confidence: 99%