X chromosome inactivation has been hypothesised to play a role in the aetiology and clinical expression of the fragile X syndrome. The identification of the FMR1 gene involved in fragile X syndrome allows testing of the assumption that the fragile X locus is normally subject to X inactivation. We studied the expression of the FMR1 gene from inactive X chromosomes by reverse transcription of RNA...

Autism is a heterogeneous condition that is likely to result from the combined effects of multiple genetic factors interacting with environmental factors. Given its complexity, the study of autism associated with Mendelian single gene disorders or known chromosomal etiologies provides an important perspective. We used microarray analysis to compare the mRNA expression profile in lymphoblastoid ...

The heterothallic fungus Podospora anserina has two mating-type alleles termed mat+ and mat-. The mat+ sequence contains one gene, FPR1, while mat- contains three genes: FMR1, SMR1, and SMR2. FPR1 and FMR1 are required for fertilization, which is followed by mitotic divisions of the two parental nuclei inside the female organ. This leads to the formation of plurinucleate cells containing a mixt...

Loss of function of the FMR1 gene leads to fragile X syndrome (FXS), the most common form of intellectual disability. The loss of FMR1 function is usually caused by epigenetic silencing of the FMR1 promoter leading to expansion and subsequent methylation of a CGG repeat in the 5' untranslated region. Very few coding sequence variations have been experimentally characterized and shown to be caus...

The strongest association between FMR1 and the ovary in humans is the increased risk of premature ovarian failure (POF) in women who carry the premutation level of CGG repeats (55-199 CGGs). Research on the FMR1 gene has extended to other endpoints of relevance in the OB/GYN setting for women, including infertility and ovarian hormones. After reviewing the nomenclature changes that have occurre...

UNLABELLED Sensory processing deficits are common in autism spectrum disorders, but the underlying mechanisms are unclear. Fragile X Syndrome (FXS) is a leading genetic cause of intellectual disability and autism. Electrophysiological responses in humans with FXS show reduced habituation with sound repetition and this deficit may underlie auditory hypersensitivity in FXS. Our previous study in ...

KEY POINTS Cortico-hippocampal feed-forward circuits formed by the temporoammonic (TA) pathway exhibit a marked increase in excitation/inhibition ratio and abnormal spike modulation functions in Fmr1 knock-out (KO) mice. Inhibitory, but not excitatory, synapse dysfunction underlies cortico-hippocampal feed-forward circuit abnormalities in Fmr1 KO mice. GABA release is reduced in TA-associated i...

Dear Editor, Patient-specific induced pluripotent stem (iPS) cells, generated from somatic cells of disease-affected individuals, hold a tremendous potential for studying disease mechanisms and for drug screening approaches using cell types previously not available (Yamanaka, 2008). Fragile-X (FX) syndrome belongs to the autism spectrum disorders, and is the most common cause of inherited menta...

Fragile X associated disorders are caused by a premutation allele in the fragile X mental retardation 1 gene (FMR1) and are hypothesized to result from the toxic effect of elevated levels of expanded FMR1 transcripts. Increased levels of FMR1 mRNA have indeed been reported in premutation carriers; however the mechanism by which expanded alleles lead to elevated levels of FMR1 mRNA in premutatio...

BACKGROUND Nearly 1% of children in the United States exhibit autism spectrum disorders, but causes and treatments remain to be identified. Mice with deletion of the fragile X mental retardation 1 (Fmr1) gene are used to model autism because loss of Fmr1 gene function causes Fragile X Syndrome (FXS) and many people with FXS exhibit autistic-like behaviors. Glycogen synthase kinase-3 (GSK3) is h...