Fragile X syndrome (FXS) is mostly caused by a CGG triplet expansion in the fragile X mental retardation 1 gene (FMR1). Up to 60% of affected males fulfill criteria for autism spectrum disorder (ASD), making FXS the most frequent monogenetic cause of syndromic ASD. It is unknown, however, whether normal variants (independent of mutations) in the fragile X gene family (FMR1, FXR1, FXR2) and in FMR2 modulate autistic features. Here, we report an accumulation model of 8 SNPs in these genes, associated with autistic traits in a discovery sample of male patients with schizophrenia (N = 692) and three independent replicate samples: patients with schizophrenia (N = 626), patients with other psychiatric diagnoses (N = 111) and a general population sample (N = 2005). For first mechanistic insight, we contrasted microRNA expression in peripheral blood mononuclear cells of selected extreme group subjects with high- versus low-risk constellation regarding the accumulation model. Thereby, the brain-expressed miR-181 species emerged as potential "umbrella regulator", with several seed matches across the fragile X gene family and FMR2. To conclude, normal variation in these genes contributes to the continuum of autistic phenotypes.
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox
The Cambridge Neurological Inventory: a clinical instrument for assessment of soft neurological signs in psychiatric patients
Gene structure and subcellular localization of FMR2, a member of a new family of putative transcription activators
Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex.
Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator
Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway
Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP
Impact of the Fragile X mental retardation 1 (FMR1) gene premutation on neuropsychiatric functioning in adult males without fragile X-associated Tremor/Ataxia syndrome: a controlled study
FancyGene: dynamic visualization of gene structures and protein domain architectures on genomic loci.
Qualitative and quantitative genotyping using single base primer extension coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MassARRAY)
Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome
The cross-sectional GRAS sample: a comprehensive phenotypical data collection of schizophrenic patients
Do social relations explain health inequalities? Evidence from a longitudinal survey in a changing eastern German region.
Sustained lentiviral-mediated overexpression of microRNA124a in the dentate gyrus exacerbates anxiety- and autism-like behaviors associated with neonatal isolation in rats
A normal genetic variation modulates synaptic MMP-9 protein levels and the severity of schizophrenia symptoms
Functional changes of AMPA responses in human induced pluripotent stem cell-derived neural progenitors in fragile X syndrome
Multiple inducers and novel roles of autoantibodies against the obligatory NMDAR subunit NR1: a translational study from chronic life stress to brain injury.
EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons
Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability
Fragile X granules are a family of axonal ribonucleoprotein particles with circuit-dependent protein composition and mRNA cargos
EGFP insertional mutagenesis reveals multiple FXR2P fibrillar states with differing ribosome association in neurons
MicroRNAs as biomarkers for psychiatric disorders with a focus on autism spectrum disorder: Current progress in genetic association studies, expression profiling, and translational research
Dysregulated Ca2+ -Permeable AMPA Receptor Signaling in Neural Progenitors Modeling Fragile X Syndrome
Are FXR Family Proteins Integrators of Dopamine Signaling and Glutamatergic Neurotransmission in Mental Illnesses?
The influence of autistic symptoms on social and non-social cognition and on real-life functioning in people with schizophrenia: Evidence from the Italian Network for Research on Psychoses multicenter study.
Autistic symptoms in people with schizophrenia: Neurocognitive, socio-cognitive, clinical and real-world functional characteristics of individuals without autistic features.
Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.
Autism: Treatment Targets
The absence of effective treatments for autism are due to the high clinical and genetic heterogeneity between affected individuals, restricted knowledge of the underlying pathophysiological mechanisms, and the lack of reliable diagnostic biomarkers. Identification of more homogenous biological subgroups is therefore essential for the development of novel treatments based on the molecular mechanisms underpinning autism and autism spectrum disorders. Find the latest research on autism treatment targets here.