Background: Diminished ovarian reserve (DOR) is a primary infertility disorder characterized by a reduction in the number and/or quality of oocytes, usually accompanied by high follicle-stimulating hormone (FSH) levels and regular menses. DOR aetiology factors are different, such as genetic factors, ageing, autoimmune disorders, adrenal gland impairment factors and iatrogenic causes, e.g. chemo...

Individuals with intellectual disability (ID) and/or neurodevelopmental disorders (NDD) are currently investigated several different approaches in clinical genetic diagnostics. To investigate the value of a genome-first approach we compared results from three diagnostic pipelines patients ID/NDD: (n=100), genome as secondary test (n=129) or chromosomal microarray (CMA) without FMR1 analysis (n=...

Background: Diminished ovarian reserve (DOR) is a heterogeneous disorder causing infertility, characterized by a decreased number of oocytes and high FSH level, the genetic cause of which is still unknown. The association between FMR1 premutations(50-200 CGG repeats) and the premature ovarian failure( POF) disease has suggested that FMR1 gene acts as a risk factor for POF and recently for DOR p...

Fragile X syndrome, the most common form of hereditary mental retardation, usually results from lack of expression of the FMR1 gene. The FMR1 protein is a cytoplasmic RNA-binding protein. The RNA-binding activity of FMR1 is an essential feature of FMR1, as fragile X syndrome can also result from the expression of mutant FMR1 protein that is impaired in RNA binding. Recently, we described two no...

Silencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs) of an unmethylated full mutation (uFM) individual with normal intelligence. The uFM fibroblast line carried an unmethylated FMR1 promoter...

Fragile X syndrome (FXS) is almost always caused by silencing of the FMR1 gene. The defects observed in FXS indicate that the normal FMR1 gene has a range of functions and plays a particularly prominent role during development. However, the mechanisms regulating FMR1 expression in vivo are not known. Here, we have tested the role of the transcription factor AP-2alpha in regulating Fmr1 expressi...

Fragile X syndrome is a neurodevelopmental disorder characterized by mild-to-severe cognitive deficits. The complete absence of Fmr1 and its protein product in the mouse model of fragile X (Fmr1 KO) provides construct validity. A major conundrum in the field is the remarkably normal performance of Fmr1 mice on cognitive tests in most reports. One explanation may be insufficiently challenging co...

Fragile X syndrome (FXS) is the most common form of inherited mental retardation. The syndrome results from the absence of the fragile X mental retardation protein (FMRP), which is encoded by the fragile X mental retardation 1 (FMR1) gene. FMR1 and its two paralogs, fragile X-related genes 1 and 2 (FXR1 and -2), form the Fmr1 gene family. Here, we examined long-lasting synaptic plasticity in Fm...

Fragile X Mental Retardation Syndrome is the most common form of hereditary mental retardation, and is caused by defects in the FMR1 gene. FMR1 is an RNA-binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. The specific function of FMR1 is not known. As a step towards understanding the function of FMR1 we sea...