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)

Methyl-CpG binding protein 2 gene (MECP2), the gene implicated in Rett syndrome, was also reported to be involved in mental retardation and autism. MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a nuclear protein family sharing the methyl-CpG binding domain (MBD) and are related to transcriptional repression. In 65 Japanese autistic patients, all the exons of each gene were screened for mutations by DHPLC, and the results were confirmed by direct sequencing. An R269C mutation that resulted in the addition of cysteine near a cysteine rich region was found in the MBD1 gene in one patient. This mutation was also detected in the patient's father with some phenotypes of autism and his normal sister, but not in 151 controls. Two repeat length polymorphisms, (GGGGCC)2 to 3 and (GGC)4 to 5, were detected in MBD2, and several polymorphisms were detected in each gene. Although our findings could not confirm that the genes of this family are responsible for the etiology in the majority of autistic patients, the R269C mutation in the MBD1 gene may relate to autism. The potential association of the high-polymorphic gene variants with autism needs to be studied further. Furthermore, these polymorphisms are useful for linkage analysis.
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PMID:Mutation analysis of methyl-CpG binding protein family genes in autistic patients. 1596 18

Mutations in MECP2, encoding methyl-CpG-binding protein 2 (MeCP2), cause the neurodevelopmental disorder Rett syndrome (RTT). Although MECP2 mutations are rare in idiopathic autism, reduced MeCP2 levels are common in autism cortex. MeCP2 is critical for postnatal neuronal maturation and a modulator of activity-dependent genes such as Bdnf (brain-derived neurotropic factor) and JUNB. The activity-dependent early growth response gene 2 (EGR2), required for both early hindbrain development and mature neuronal function, has predicted binding sites in the promoters of several neurologically relevant genes including MECP2. Conversely, MeCP2 family members MBD1, MBD2 and MBD4 bind a methylated CpG island in an enhancer region located in EGR2 intron 1. This study was designed to test the hypothesis that MECP2 and EGR2 regulate each other's expression during neuronal maturation in postnatal brain development. Chromatin immunoprecipitation analysis showed EGR2 binding to the MECP2 promoter and MeCP2 binding to the enhancer region in EGR2 intron 1. Reduction in EGR2 and MeCP2 levels in cultured human neuroblastoma cells by RNA interference reciprocally reduced expression of both EGR2 and MECP2 and their protein products. Consistent with a role of MeCP2 in enhancing EGR2, Mecp2-deficient mouse cortex samples showed significantly reduced EGR2 by quantitative immunofluorescence. Furthermore, MeCP2 and EGR2 show coordinately increased levels during postnatal development of both mouse and human cortex. In contrast to age-matched Controls, RTT and autism postmortem cortex samples showed significant reduction in EGR2. Together, these data support a role of dysregulation of an activity-dependent EGR2/MeCP2 pathway in RTT and autism.
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PMID:Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism. 1900 Sep 91

Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome. We hypothesized that mutations in other members of the methyl-CpG-binding domain (MBD) family may also cause autistic features in individuals. We evaluated 226 autistic individuals for alterations in the four genes most homologous to MECP2: MBD1, MBD2, MBD3, and MBD4. A total of 46 alterations were identified in the four genes, including ten missense changes and two deletions that alter coding sequence. Several are either unique to our autistic population or cosegregate with affected individuals within a family, suggesting a possible relation of these variations to disease etiology. Variants include a R23M alteration in two affected half brothers which falls within the MBD domain of the MBD3 protein, as well as a frameshift in MBD4 that is predicted to truncate almost half of the protein. These results suggest that rare cases of autism may be influenced by mutations in members of the dynamic MBD protein family.
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PMID:Novel variants identified in methyl-CpG-binding domain genes in autistic individuals. 1992 Dec 86