Fragile X-Linked Mental Retardation

Gantois, Ilse; Kooy, R. Frank; Oostra, Ben A.

doi:10.1002/3527600906.mcb.200300051

Cited by 2 publications

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“…According to estimates, 1–3% of the human population has an IQ below 70 1 2. Fragile X syndrome is the main cause of inherited mental retardation and the leading known genetic form of autism affecting 1/2500 individuals, according to the latest estimates 3 4 5. Cognitive dysfunction in fragile X syndrome includes deficiencies in working and short term memory, executive function, and mathematic and visuospatial abilities 6 7 8.…”

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confidence: 99%

Fragile X syndrome: from molecular genetics to therapy

D’Hulst

Kooy

2009

Journal of Medical Genetics

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International audienceFragile X syndrome, the main cause of inherited mental retardation, is caused by transcriptional silencing of the , . Absence of the associated protein FMRP leads to the dysregulation of many genes creating a phenotype of ADHD, anxiety, epilepsy and autism. The core aim of this review is to discuss two decades of molecular research leading to the characterisation of cellular and molecular pathways involved in the pathology of this disease and as a consequence to the identification of two new promising targets for rational therapy of fragile X syndrome, namely the group 1 metabotrope glutamate receptors (Gp1 mGluRs) and the gamma-amino butyric acid A receptors (GABA(A)Rs). As no current clinical treatments for fragile x syndrome are directed specifically at the underlying neuronal defect due to absence of FMRP, this might open new powerful therapeutic strategies

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confidence: 99%

Fragile X syndrome: from molecular genetics to therapy

D’Hulst

Kooy

2009

Journal of Medical Genetics

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“…Fragile X syndrome is the leading cause of inherited mental retardation and developmental disabilities with an incidence of 1 in 4000-6000 (Gantois et al, 2004 ;Penagarikano et al, 2007). Fragile X patients have a significant intellectual disability that may vary from mild to severe.…”

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confidence: 99%

Effect of genetic background on acoustic startle response in fragile X knockout mice

et al. 2008

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To study the effect of genetic background on the Fmr1 knockout mutation in mice, we compared the acoustic startle response (ASR) of male fragile X knockout mice bred in three different genetic backgrounds, including C57BL/6J (C57BL/6J x 129P2/OlaHsd) F1 and F2 intercross. ASR is used as a behavioural tool to assess the neuronal basis of behavioural plasticity. For each background studied, fragile X knockouts clearly differed in ASR from their control littermates. C57BL/6J knockouts showed an increase in ASR in response to the lowest stimulus of 90 dB and a decrease in ASR in response to the highest stimulus of 110 dB when compared with control mice, whereas knockouts of the F1 generation showed significantly lower ASRs for all the three stimulus intensities used when compared with control littermates. These data demonstrate that the expression of the fragile X phenotype in ASR of fragile X knockout mice may be influenced by the presence of 129 genes in the genetic background and that modifier genes may influence the fragile X phenotype. Surprisingly, and in contrast with knockouts of the F1 generation that showed a decreased ASR, knockouts of the F2 generation showed a significantly increased ASR compared with their control littermates. This is especially remarkable as both F1 and F2 mice consist of 50% of the genetic material from each of the parental strains C57BL/6J and 129P2/OlaHsd strain. Thus, the different distribution of the genetic background seems to be responsible for the difference in ASR between F1 and F2. This opposite ASR in the F1 and F2 generations is unique in behavioural studies and has, to our knowledge, not been previously reported.

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Fragile X-Linked Mental Retardation

Cited by 2 publications

References 205 publications

Fragile X syndrome: from molecular genetics to therapy

Fragile X syndrome: from molecular genetics to therapy

Effect of genetic background on acoustic startle response in fragile X knockout mice

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