Fragile X Syndrome Research Today is a free monthly online journal that collates and summarizes the latest research about Fragile X Syndrome, including details on symptoms, treatment, heritability, diagnosis.

Alteration of expression of muscle-specific isoforms of the Fragile X Related Protein 1 (FXR1P) in facio-scapulohumeral muscular distrophy patients.

Davidovic L, Sacconi S, Bechara E, Delplace S, Allegra M, Desnuelle C, Bardoni B

CNRS UMR6097, France.

The Fragile X Mental Retardation-Related 1 (FXR1) gene belongs to the Fragile X Related family, that also include the Fragile X Mental retardation (FMR1) gene involved in Fragile X syndrome, the most common form of inherited mental retardation. While the absence of FMRP impairs cognitive functions, inactivation of FXR1 has been reported to have drastic effects in mouse and xenopus myogenesis. Seven alternatively spliced FXR1 mRNA variants have been identified, three of them being muscle-specific. Interestingly, they encode FXR1P isoforms displaying selective RNA-binding properties. Since Facio-ScapuloHumeral muscular Dystrophy (FSHD) is an inherited myopathy characterized by altered splicing of mRNAs encoding muscle-specific proteins, we have studied the splicing pattern of FXR1 mRNA in myoblasts and myotubes of FSHD patients. We show here that FSHD-affected myoblasts display an abnormal pattern of expression of FXR1P isoforms. Moreover, we provide evidence that this altered pattern of expression is due to a specific reduced stability of muscle-specific FXR1 mRNA variants, leading to a reduced expression of FXR1P muscle-specific isoforms. Our data suggest that the molecular basis of FSHD not only involves splicing alterations, as previously proposed, but may also involve a deregulation of mRNA stability. In addition, since FXR1P is an RNA-binding protein likely to regulate the metabolism of muscle-specific mRNAs during myogenesis, its altered expression in FSHD myoblasts may contribute to the physiopathology of this disease.

Published 16 July 2008 in J Med Genet.
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Articles on Fragile X Syndrome published 16 July 2008:

A model for offering carrier screening for fragile X syndrome to nonpregnant women: results from a pilot study.   Genet Med, 10(7): 525-35.

PURPOSE: To develop a model of offering population carrier screening for fragile X syndrome to nonpregnant women in primary care, using a program evaluation framework. METHODS: A three-phase approach included: (I) needs assessment exploring staff and client attitudes, and informing development of educational materials, questionnaires and protocols; (II) offering screening to women, with questionnaires at baseline (Q1) and another (Q2) 1-month later; (III) genetic counseling for test-positive ... [Abstract] [Full-text]

Epigenetic analysis reveals a euchromatic configuration in the FMR1 unmethylated full mutations.   Eur J Hum Genet.

Fragile X syndrome (FXS) is caused by the expansion of a CGG repeat in the 5'UTR of the FMR1 gene and the subsequent methylation of all CpG sites in the promoter region. We recently identified, in unrelated FXS families, two rare males with an unmethylated full mutation, that is, with an expanded CGG repeat (>200 triplets) lacking the typical CpG methylation in the FMR1 promoter. These individuals are not mentally retarded and do not appear to be mosaic for premutation or methylated full ... [Abstract] [Full-text]

Articles on Fragile X Syndrome published 15 July 2008:

Secondary medical diagnosis in fragile X syndrome with and without autism spectrum disorder.   Am J Med Genet A.

This study examined whether secondary medical diagnoses that affect CNS function (i.e., seizures, malformations, or genetic disorders), are more likely to occur in individuals with fragile X syndrome (FXS) and autism spectrum disorder (FXS + ASD) or FXS alone. Ninety males (3-25 years) with FXS or FXS + ASD were evaluated for secondary medical diagnoses by medical history and examination. A significant difference in the incidence of medical problems was found between patients with FXS + ASD ... [Abstract] [Full-text]

Articles on Fragile X Syndrome published 14 July 2008:

Temporal requirements of the fragile X mental retardation protein in the regulation of synaptic structure.   Development, 135(15): 2637-48.

Fragile X syndrome (FraX), caused by the loss-of-function of one gene (FMR1), is the most common inherited form of both mental retardation and autism spectrum disorders. The FMR1 product (FMRP) is an mRNA-binding translation regulator that mediates activity-dependent control of synaptic structure and function. To develop any FraX intervention strategy, it is essential to define when and where FMRP loss causes the manifestation of synaptic defects, and whether the reintroduction of FMRP can ... [Abstract] [Full-text]

Articles on Fragile X Syndrome published 11 July 2008:

Unaltered hormonal response to stress in a mouse model of fragile X syndrome.   Psychoneuroendocrinology, 33(6): 883-9.

Reports in the clinical literature and studies of fmr1 knockout mice have led to the hypothesis that, in addition to mental retardation, fragile X syndrome is characterized by a dysregulation of hypothalamic-pituitary-adrenal axis function. We have systematically examined this hypothesis by studying the effects of stress on adrenocorticotrophic hormone and corticosterone levels in adult, male fmr1 knockout mice. Initially we determined the circadian rhythms of the plasma hormone levels in both ... [Abstract] [Full-text]

Altered hypothalamus-pituitary-adrenal gland axis regulation in the expanded CGG-repeat mouse model for fragile X-associated tremor/ataxia syndrome.   Psychoneuroendocrinology, 33(6): 863-73.

The human FMR1 gene contains an unstable CGG-repeat in its 5' untranslated region. The repeat length in the normal population is polymorphic (5-54 CGG-repeats). Individuals carrying lengths beyond 200 CGGs (i.e. the full mutation) show hypermethylation and as a consequence gene silencing of the FMR1 gene. The absence of the gene product FMRP causes the fragile X syndrome, the most common inherited form of mental retardation. Elderly carriers of the premutation (PM), which is defined as a repeat ... [Abstract] [Full-text]

Savings and Extinction of Conditioned Eyeblink Responses in Fragile X Syndrome.   Genes Brain Behav.

The fragile X syndrome is the most widespread heritable form of mental retardation caused by the lack of expression of the fragile X mental retardation protein. This lack has been related to deficits in cerebellum-mediated acquisition of conditioned eyelid responses in individuals with fragile X syndrome. In the current behavioral study long term effects of deficiency of fragile X mental retardation protein were investigated, by examining the acquisition, savings and extinction of delay ... [Abstract] [Full-text]

Articles on Fragile X Syndrome published 10 July 2008:

Fragile X syndrome associated with tic disorders.   Mov Disord, 23(8): 1108-12.

Movement disorders other than late onset tremor-ataxia in association with fragile X syndrome, the most common identifiable cause of inherited mental retardation, seem to be rare. Here we describe five male patients from three unrelated families with fragile X syndrome that presented with motor and phonic tics. Clinically, 4 patients fulfilled diagnostic criteria for Gilles de la Tourette syndrome (GTS) while 1 patient would have been diagnosed with an adult onset tic disorder. However, in all ... [Abstract] [Full-text]

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