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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present here a unique case of a 14-year-old female with autism and some features similar to Rett syndrome (RTT). Genetic analysis demonstrated a large deletion of chromosome 2q instead of a MECP2 mutation. Like a Rett patient, she is dyspraxic and shows frequent hand-washing stereotypic activities, hyperpnea, and bruxism. Like a preserved speech variant (PSV) of RTT, she is obese, able to speak in second and third persons, frequently echolalic, and has final normal head circumference and autistic behavior. In addition, she has dysmorphic features such as down-slanting palpebral fissures, low set ears without lobuli, bilateral flat feet, and bilateral syndactyly of the second and third toes, which do not belong to the Rett spectrum. She has a de novo chromosomal deletion in 2q34 of paternal origin. Gene content analysis of the deleted region showed the presence of 47 genes (14 putative and 33 known genes). This region contains some interesting genes such as ADAM23/MDC3, CREB1, KLF7, and MAP2. Because alteration of neuronal maturation, dendritic anomalies, and a decrease in MAP2 immunoreactivity in white matter neurons are well documented in RTT patients, we propose MAP2 gene as a good candidate for the generation of PSV phenotype in this case.
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PMID:Chromosome 2 deletion encompassing the MAP2 gene in a patient with autism and Rett-like features. 1498 29

Autism and Rett syndrome, a severe neurological disorder with autistic behavior, are classified as separate disorders on clinical and etiological ground. Rett syndrome is a monogenic X-linked dominant condition due to de novo mutations in the MECP2 gene, whereas autism is a neurodevelopmental and behavioral disorder with complex genetic basis. Maternally inherited duplications on 15q11-q13 are found in a fraction of autistic children suggesting that an abnormal dosage of gene(s) within this region might cause susceptibility to autism. Now we show that three Rett patients are carriers of both a MECP2 mutation and a 15q11-q13 rearrangement, suggesting that there might be a relationship between autism-related genes and the MECP2 gene.
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PMID:Three Rett patients with both MECP2 mutation and 15q11-13 rearrangements. 1506 58

Rett syndrome (RTT) is a severe neurodevelopmental disorder with features of autism that results from mutation of the gene encoding the transcriptional repressor methyl-CpG binding protein (MECP2). The consequences of loss of a transcription factor may be complex, affecting the expression of many proteins, thus limiting understanding of this class of diseases and impeding therapeutic strategies. This is true for RTT. Neither the cell biological mechanism(s) nor the developmental stage affected by MECP2 deficiency is known. In vivo analysis of the olfactory system demonstrates that Mecp2 deficiency leads to a transient delay in the terminal differentiation of olfactory neurons. This delay in maturation disrupts axonal targeting in the olfactory bulb, resulting in abnormal axonal projections, subglomerular disorganization, and a persistent reduction in glomerular size. These results indicate a critical cell biological function for Mecp2 in mediating the final stages of neuronal development.
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PMID:The transcriptional repressor Mecp2 regulates terminal neuronal differentiation. 1534 42

Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females. Regression is a defining feature of RTT. During the regression stage, RTT girls display many autistic features, such as loss of communication and social skills, poor eye contact, and lack of interest, and initially may be given the diagnosis of autism. The discovery of the genetic cause of RTT, mutations in the MECP2 gene, a transcriptional repressor, has promoted the early diagnosis of RTT and development of mouse models. The phenotype of one mouse model includes features such as regression and abnormal behavioral and social interactions. The timing of the period of regression in RTT--during ages 1 to 2 years--parallels the period of intense synaptic development. The effects of the MECP2 mutation also increases concomitantly with peak synaptogenesis. Neuropathological findings in Rett include the selective reduction of dendritric spines in the pyramidal cells of RTT brains; this feature has also been reported in autism. Studies have observed that MECP influences the expression of brain-derived neurotrophic factor and thus may influence synaptic plasticity. Abnormalities in synapse maintenance and modulation may contribute to regression in RTT and autism. Studies of the clinical aspects of the regression period and of the mouse model may be useful in understanding the pathophysiology of RTT and other neurodevelopmental disorders such as autism. A recent study observed abnormal expression of MeCP2 in RTT and other neurodevelopmental disorders such as autism. Although the genetic background and certain clinical features differ in RTT and autism, a similar mechanism involving MeCP2 regulation and expression may contribute to regression.
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PMID:Rett syndrome: of girls and mice--lessons for regression in autism. 1536 75

Autism is a common neurodevelopmental disorder of complex genetic etiology. Rett syndrome, an X-linked dominant disorder caused by MECP2 mutations, and Angelman syndrome, an imprinted disorder caused by maternal 15q11-q13 or UBE3A deficiency, have phenotypic and genetic overlap with autism. MECP2 encodes methyl-CpG-binding protein 2 that acts as a transcriptional repressor for methylated gene constructs but is surprisingly not required for maintaining imprinted gene expression. Here, we test the hypothesis that MECP2 deficiency may affect the level of expression of UBE3A and neighboring autism candidate gene GABRB3 without necessarily affecting imprinted expression. Multiple quantitative methods were used including automated quantitation of immunofluorescence and in situ hybridization by laser scanning cytometry on tissue microarrays, immunoblot and TaqMan PCR. The results demonstrated significant defects in UBE3A/E6AP expression in two different Mecp2 deficient mouse strains and human Rett, Angelman and autism brains compared with controls. Although no difference was observed in the allelic expression of several imprinted transcripts in Mecp2-null brain, Ube3a sense expression was significantly reduced, consistent with the decrease in protein. A non-imprinted gene from 15q11-q13, GABRB3, encoding the beta3 subunit of the GABAA receptor, also showed significantly reduced expression in multiple Rett, Angelman and autism brain samples, and Mecp2 deficient mice by quantitative immunoblot. These results suggest an overlapping pathway of gene dysregulation within 15q11-q13 in Rett, Angelman and autism and implicate MeCP2 in the regulation of UBE3A and GABRB3 expressions in the postnatal mammalian brain.
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PMID:Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. 1561 69

Rett syndrome (RTT), caused by mutations in MECP2 (encoding methyl CpG binding protein 2), and Angelman syndrome (AS), caused by maternal deficiency of chromosome 15q11-13, are autism-spectrum neurodevelopmental disorders. MeCP2 is a transcriptional repressor of methylated genes, but MECP2 mutation does not directly affect the imprinted expression of genes within 15q11-13. We tested a potential role for MeCP2 in the homologous pairing of imprinted 15q11-13 alleles in human brain tissue and differentiated neurons by fluorescence in situ hybridization (FISH). FISH analysis of control cerebral samples demonstrated a significant increase in homologous pairing specific to chromosome 15 from infant to juvenile brain samples. Significant and specific deficiencies in the percentage of paired chromosome 15 alleles were observed in RTT, AS and autism brain samples when compared with normal controls. SH-SY5Y neuroblastoma cells also showed a significant and specific increase in the percentage of chromosome 15q11-13 paired alleles following induced differentiation in vitro. Transfection with a methylated oligonucleotide decoy specifically blocked binding of MeCP2 to the SNURF/SNRPN promoter within 15q11-13 and significantly lowered the percentage of paired 15q11-13 alleles in SH-SY5Y cells. These combined results suggest a role for MeCP2 in chromosome organization in the developing brain and provide a potential mechanistic association between several related neurodevelopmental disorders.
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PMID:Homologous pairing of 15q11-13 imprinted domains in brain is developmentally regulated but deficient in Rett and autism samples. 1568 52

Autism is a heterogeneous disorder that can reveal a specific genetic disease. This paper describes several genetic diseases consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, duplication of 15q11-q13, Down syndrome, San Filippo syndrome, MECP2 related disorders, phenylketonuria, Smith-Magenis syndrome, 22q13 deletion, adenylosuccinate lyase deficiency, Cohen syndrome, and Smith-Lemli-Opitz syndrome) and proposes a consensual and economic diagnostic strategy to help practitioners to identify them. A rigorous initial clinical screening is presented to avoid unnecessary laboratory and imaging studies. Regarding psychiatric nosography, the concept of "syndromal autism"--autism associated with other clinical signs should be promoted because it may help to distinguish patients who warrant a multidisciplinary approach and further investigation.
J Autism Dev Disord 2005 Feb
PMID:Specific genetic disorders and autism: clinical contribution towards their identification. 1579 26

The higher prevalence of autism in males than in females suggests the possible involvement of the X chromosome. To test the hypothesis that there are mutations increasing susceptibility to autism on the X chromosome, and in particular the distal portion of the long arm that encompasses the FMRI and MECP2 loci, a genetic linkage study was performed. Twenty-two fragile X-negative families multiplex for autism and related disorders were used for the study. Linkage analysis, for markers in the Xq27-q28 region, using model-free likelihood-based analysis, produced a maximum MLOD of 1.7 for the narrowest diagnostic category of the typical autism/severe autism spectrum, and nonparametric analysis produced a maximum non-parametric lod (NPL) score of 2.1 for a broad phenotype diagnostic model. Thus, this study offers modest support for a susceptibility locus for autism within the Xq27-q28 region. Further genetic investigations of this region are warranted.
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PMID:Genetic linkage analysis of the X chromosome in autism, with emphasis on the fragile X region. 1590 Feb 22

Rett syndrome is a leading cause of postnatal neurodevelopmental regression. Rett syndrome is caused by mutations in MECP2, the gene encoding methyl-CpG binding protein 2. In up to 96% of all classic cases, Rett syndrome cases are caused by mutations or deletions in MECP2. The phenotypic spectrum of MECP2 mutations is broad and includes mental retardation with or without seizures, Angelman syndrome-like phenotype, and autism. Mecp308/Y mice carry a truncating mutation and display many of the features seen in Rett syndrome. Social behavior abnormalities and impaired social interactions in Mecp308/Y mice suggest that MeCP2 plays a role in modulating the activity of genes and neurons important for social interactions. Mice that overexpress MeCP2 at twice the endogenous levels develop a progressive neurologic disorder, demonstrating that MeCP2 levels are tightly regulated and raising the possibility that duplications or gain-of-function mutations of MECP2 might underlie some cases of neurodevelopmental X-linked disorders.
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PMID:MeCP2 dysfunction in humans and mice. 1622 28

Rett syndrome (RTT) is a postnatal neurodevelopmental disorder characterized by the loss of acquired motor and language skills, autistic features, and unusual stereotyped movements. RTT is caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). Mutations in MECP2 cause a variety of neurodevelopmental disorders including X-linked mental retardation, psychiatric disorders, and some cases of autism. Although MeCP2 was identified as a methylation-dependent transcriptional repressor, transcriptional profiling of RNAs from mice lacking MeCP2 did not reveal significant gene expression changes, suggesting that MeCP2 does not simply function as a global repressor. Changes in expression of a few genes have been observed, but these alterations do not explain the full spectrum of Rett-like phenotypes, raising the possibility that additional MeCP2 functions play a role in pathogenesis. In this study, we show that MeCP2 interacts with the RNA-binding protein Y box-binding protein 1 and regulates splicing of reporter minigenes. Importantly, we found aberrant alternative splicing patterns in a mouse model of RTT. Thus, we uncovered a previously uncharacterized function of MeCP2 that involves regulation of splicing, in addition to its role as a transcriptional repressor.
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PMID:Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. 1625 Dec 72


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