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)

Intellectual and developmental disabilities (IDDs) such as autistic spectrum disorders (ASDs) and epilepsies are heterogeneous disorders that have diverse etiologies and pathophysiologies. The high rate of co-occurrence of these disorders, however, suggests potentially shared underlying mechanisms. A number of well-known genetic disorders share epilepsy, intellectual disability, and autism as prominent phenotypic features, including tuberous sclerosis complex, Rett syndrome, and fragile X syndrome. In addition, mutations of several genes involved in neurodevelopment, including ARX, DCX, neuroligins, and neuropilin 2 have been identified in children with epilepsy, IDDs, ASDs, or a combination of thereof. Finally, in animal models, early life seizures can result in cellular and molecular changes that could contribute to learning and behavioral disabilities. Increased understanding of the common genetic, molecular, and cellular mechanisms of IDDs, ASDs, and epilepsy may provide insight into their underlying pathophysiology and elucidate new therapeutic approaches for these conditions.
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PMID:Molecular mechanisms of cognitive and behavioral comorbidities of epilepsy in children. 2121 35

Autism and epilepsy are diseases which have complex genetic inheritance. Genome-wide association and other genetic studies have implicated at least 500+ genes associated with the occurrence of autism spectrum disorders (ASD) including the human semaphorin 3F (Sema 3F) and neuropilin 2 (NRP2) genes. However, the genetic basis of the comorbid occurrence of autism and epilepsy is unknown. The aberrant development of GABAergic circuitry is a possible risk factor in autism and epilepsy. Molecular biological approaches were used to test the hypothesis that cell-specific genetic variation in mouse homologs affects the formation and function of GABAergic circuitry. The empirical analysis with mice homozygous null for one of these genes, Sema 3F, in GABAergic neurons substantiated these predictions. Notably, deletion of Sema 3F in interneurons but not excitatory neurons during early development decreased the number of interneurons/neurites and mRNAs for cell-specific GABAergic markers and increased epileptogenesis and autistic behaviors. Studies of interneuron cell-specific knockout of Sema 3F signaling suggest that deficient Sema 3F signaling may lead to neuroinflammation and oxidative stress. Further studies of mouse KO models of ASD genes such as Sema 3F or NRP2 may be informative to clinical phenotypes contributing to the pathogenesis in autism and epilepsy patients.
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PMID:Deletion of Semaphorin 3F in Interneurons Is Associated with Decreased GABAergic Neurons, Autism-like Behavior, and Increased Oxidative Stress Cascades. 3063 60