Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a nondysmorphic patient with developmental delay and autism spectrum disorder who has a missense mutation in the Jumonji AT-rich interactive domain 1C (JARID1C) gene. This child first presented at 30 months of age with stereotyped and repetitive behaviors, impairment in social reciprocity and in the use of multiple nonverbal behaviors, and developmental delay primarily in the language domain. A diagnosis of autism was made and subsequently confirmed at the current age of 47 months. Cytogenetic and fragile X studies were normal. Mutational analysis revealed a novel missense mutation in exon 16 of the JARID1C gene that results in an arginine to tryptophan substitution at amino acid 766 (R766W). Sequence alignment analysis with multiple available eukaryotic sequences including the homologous proteins of mouse and zebrafish demonstrated that the affected amino acid is conserved. JARID1C has not previously been implicated in autism susceptibility. Recent novel molecular evidence suggests that it is a histone demethylase specific for di- and trimethylated histone 3 lysine 4 (H3K4) and functions as a transcriptional repressor by fostering REST-mediated neuronal gene regulation. The JARID1C-regulated genes SCN2A, CACNA1H, BDNF, and SLC18A1 have previously been associated with autism and cognitive dysfunction. This patient brings the total number of reported JARID1C mutations to 14. This presentation both extends the range of neurocognitive phenotypes attributable to mutations in this gene and illustrates the importance of molecular studies and DNA sequence analysis for accurate diagnosis of monogenic causes of autism.
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PMID:A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD). 1820 67

Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20, FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1 and VMAT1/SLC18A1) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (Fgf17) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence.
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PMID:Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. 1920 25