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.

Preparation and validation of the first WHO international genetic reference panel for Fragile X syndrome.

Hawkins M, Boyle J, Wright KE, Elles R, Ramsden SC, O'Grady A, Sweeney M, Barton DE, Burgess T, Moore M, Burns C, Stacey G, Gray E, Metcalfe P, Hawkins JR

National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts, UK.

Fragile X syndrome is the most common inherited form of mental retardation. It is caused by expansion of a trinucleotide (CGG)n repeat sequence in the 5' untranslated region of the FMR1 gene, resulting in promoter hypermethylation and suppression of FMR1 transcription. Additionally, pre-mutation alleles in carrier males and females may result in Fragile X tremor ataxia syndrome and primary ovarian insufficiency, respectively. Fragile X is one of the most commonly requested molecular genetic tests worldwide. Quality assessment schemes have identified a wide disparity in allele sizing between laboratories. It is therefore important that clinical laboratories have access to characterized reference materials (RMs) to aid accurate allele sizing and diagnosis. With this in mind, a panel of genotyping RMs for Fragile X syndrome has been developed, which should be stable over many years and available to all diagnostic laboratories. Immortalized cell lines were produced by Epstein-Barr virus transformation of lymphocytes from consenting patients. Genomic DNA was extracted in bulk and RM aliquots were freeze-dried in glass ampoules. Twenty-one laboratories from seventeen countries participated in a collaborative study to assess their suitability. Participants evaluated the samples (blinded, in triplicate) in their routine methods alongside in-house and commercial controls. The panel of five genomic DNA samples was endorsed by the European Society of Human Genetics and approved as an International Standard by the Expert Committee on Biological Standardization at the World Health Organization.European Journal of Human Genetics advance online publication, 25 August 2010; doi:10.1038/ejhg.2010.135.

Published 25 August 2010 in Eur J Hum Genet.
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Articles on Fragile X Syndrome published 25 August 2010:

PGD for fragile X syndrome: ovarian function is the main determinant of success.   Hum Reprod.

BACKGROUND PGD for fragile X syndrome (FRAX) is inefficient, probably owing to fewer oocytes, poor embryo quality and difficulties in genetic analysis. We investigated IVF-PGD in FRAX mutation carriers compared with controls, looking at the effects of oocyte and embryo number/quality on live birth outcome. METHODS We performed IVF-PGD in 27 patients with the FRAX mutation and 33 controls with other genetic diseases. Genetic testing was by multiplex PCR. RESULTS Seventy-nine and 108 IVF-PGD ... [Abstract] [Full-text]

Articles on Fragile X Syndrome published 24 August 2010:

Developmental characteristics of dendritic spines in the dentate gyrus of Fmr1 knockout mice.   Brain Res.

Fragile X Syndrome (FXS) is the most common form of inherited mental retardation. The neuroanatomical phenotype of adult FXS patients, as well as adult Fmr1 knockout (KO) mice, includes elevated dendritic spine density and a spine morphology profile in neocortex that resembles younger individuals. Developmental studies in mouse neocortex have revealed a dynamic phenotype that varies with age, especially during the period of synaptic pruning. Here we investigated the hippocampal dentate gyrus to ... [Abstract] [Full-text]

Autism in Fragile X Syndrome: A Category Mistake?   J Am Acad Child Adolesc Psychiatry, 49(9): 921-933.

OBJECTIVE: Many investigators now routinely classify children with fragile X syndrome (FXS) according to whether or not they also meet diagnostic criteria for autism. To determine whether this classification is appropriate, we examined the profiles of autistic behaviors shown by boys and girls with FXS. METHOD: Individuals with FXS, aged 5 to 25 years, were assessed on two established measures of autism, the Social Communication Questionnaire (SCQ) and the Autism Diagnostic Observation Schedule ... [Abstract] [Full-text]

Articles on Fragile X Syndrome published 23 August 2010:

In vivo brain anatomy of adult males with Fragile X syndrome: An MRI study.   Neuroimage.

Fragile X Syndrome (FraX) is caused by the expansion of a single trinucleotide gene sequence (CGG) on the X chromosome, and is a leading cause of learning disability (mental retardation) worldwide. Relatively few studies, however, have examined the neuroanatomical abnormalities associated with FraX. Of those that are available many included mixed gender populations, combined FraX children and adults into one sample, and employed manual tracing techniques which measures bulk volume of particular ... [Abstract] [Full-text]

Articles on Fragile X Syndrome published 20 August 2010:

FMR1 protein expression in blood smears for fragile x syndrome diagnosis in a mexican population sample.   Genet Test Mol Biomarkers, 14(4): 511-4.

Molecular diagnosis of fragile X syndrome (FXS) is carried out by Southern blot or polymerase chain reaction-Southern analysis; however, these procedures are expensive and time consuming, making it impractical for mass screening programs. Willemsen et al. developed and tested the diagnostic potential of a rapid antibody test on blood smears, based on the presence of fragile X mental retardation protein (FMRP) in peripheral lymphocytes from normal individuals and its absence in male patients ... [Abstract] [Full-text]

Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders.   Pharmacol Ther.

Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium's therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurotrophic properties against various insults, and considerable clinical potential for the treatment of several neurodegenerative conditions. Evidence from pharmacological and gene ... [Abstract] [Full-text]

Articles on Fragile X Syndrome published 19 August 2010:

Physiological Activation of Synaptic Rac>PAK (p-21 Activated Kinase) Signaling Is Defective in a Mouse Model of Fragile X Syndrome.   J Neurosci, 30(33): 10977-84.

The abnormal spine morphology found in fragile X syndrome (FXS) is suggestive of an error in the signaling cascades that organize the actin cytoskeleton. We report here that physiological activation of the small GTPase Rac1 and its effector p-21 activated kinase (PAK), two enzymes critically involved in actin management and functional synaptic plasticity, is impaired at hippocampal synapses in the Fmr1-knock-out (KO) mouse model of FXS. Theta burst afferent stimulation (TBS) caused a marked ... [Abstract] [Full-text]

Articles on Fragile X Syndrome published 17 August 2010:

Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein.   Proc Natl Acad Sci U S A.

Fragile X syndrome is caused by the absence of functional fragile X mental retardation protein (FMRP), an RNA binding protein. The molecular mechanism of aberrant protein synthesis in fmr1 KO mice is closely associated with the role of FMRP in mRNA transport, delivery, and local protein synthesis. We show that GFP-labeled Fmr1 and CaMKIIalpha mRNAs undergo decelerated motion at 0-40 min after group I mGluR stimulation, and later recover at 40-60 min. Then we investigate targeting of mRNAs ... [Abstract] [Full-text]

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