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

Autism and Rett syndrome (RS) are both developmental disorders of unknown origin. Autism is a behaviourally defined syndrome. RS, which affects girls only, is characterized by a profound learning disability following early normal development, with a consistent cluster of clinical features. Differentiation of RS from infantile autism in the very early stages of the disorders is not always easy. Both syndromes still lack discriminative laboratory markers for accurate diagnosis and differentiation. We decided to compare the CSF nerve-growth factor (NGF) levels of children with infantile autism and children with RS using enzyme-linked immunosorbent assay (ELISA). Our findings of mainly normal CSF NGF in autism and low to negligible values in RS are in agreement with the different morphological and neurochemical findings (brain growth, affected brain areas, neurotransmitter metabolism) in the two syndromes. CSF NGF could be used as a biochemical marker for differentiation of patients with autism from those with RS.
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PMID:Levels of cerebrospinal fluid nerve-growth factor differ in infantile autism and Rett syndrome. 1021 Feb 46

Entorhinal cortex (EC), fascia dentata (FD), hippocampus (HP), and basal ganglia (BG) were studied in Rett syndrome (RS) cases and compared with control brains and an autism case. Kluver-Barrera and Golgi methods were used. In RS most of the areas of EC, HP, and FD showed severe cell hypochromia. In the EC all cells of layer II and most in layer III were in a state of total chromatolysis or were "ghost" cells, but the cells of layers V and VI were preserved and moderately hyperchromic. In FD and HP the majority of the granular cells and cells of CA3 and CA4 fields were severely hypochromic, whereas in the CA1 field most cells were normal or slightly hypercaryochromic. In BG mostly mild or moderate aberration from normal cell structure was observed: in striatum, mild hypercaryochromia of small neurons and more expressive hyperchromia of large neurons were found; and in pallidum, mild or moderate hypercaryochromia to severe hyperchromia in pallidum internum was found. Degeneration of thick myelinated fibers was evident in pallidum. Large striatal and pallidal neurons showed signs of constructive changes in Golgi slices. These data allow the determination of the cause of the main symptoms of RS. The motor disorders, including specific stereotyped movements, could be related to the enhanced activity of BG cells due to their deafferentation from the side of the neocortex and to supposed hyperactivity of the EC-striatal pathway; the mental retardation and epileptic seizures could be due to FD-HP involvement.
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PMID:Morphological study of the entorhinal cortex, hippocampal formation, and basal ganglia in Rett syndrome patients. 1034 23

Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females, with an incidence of 1 in 10,000-15,000 (ref. 2). Patients with classic RTT appear to develop normally until 6-18 months of age, then gradually lose speech and purposeful hand use, and develop microcephaly, seizures, autism, ataxia, intermittent hyperventilation and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood. As RTT occurs almost exclusively in females, it has been proposed that RTT is caused by an X-linked dominant mutation with lethality in hemizygous males. Previous exclusion mapping studies using RTT families mapped the locus to Xq28 (refs 6,9,10,11). Using a systematic gene screening approach, we have identified mutations in the gene (MECP2 ) encoding X-linked methyl-CpG-binding protein 2 (MeCP2) as the cause of some cases of RTT. MeCP2 selectively binds CpG dinucleotides in the mammalian genome and mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A (refs 12,13). In 5 of 21 sporadic patients, we found 3 de novo missense mutations in the region encoding the highly conserved methyl-binding domain (MBD) as well as a de novo frameshift and a de novo nonsense mutation, both of which disrupt the transcription repression domain (TRD). In two affected half-sisters of a RTT family, we found segregation of an additional missense mutation not detected in their obligate carrier mother. This suggests that the mother is a germline mosaic for this mutation. Our study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
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PMID:Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. 1050 98

A possible role of the immune system in the pathogenesis of some neurologic disorders, including infantile autism, was recently postulated. This observation prompted the authors to investigate some immunologic aspects in a group of patients with Rett syndrome, a disorder still not completely clarified but with some points of commonality with infantile autism. Humoral and cell-mediated immunity were investigated in 20 females with Rett syndrome. Peripheral lymphocyte subsets revealed a reduced percentage of CD8+ suppressor-cytotoxic cells in all of the patients with Rett syndrome, resulting in an increased CD4+/CD8+ ratio. In addition, 15 (75%) of the 20 patients had low levels of natural killer cells. Soluble interleukin-2 receptor was elevated in the youngest patients. Antineuronal and antimyelin ganglioside antibodies were absent, as were antinuclear antibodies, antistriated muscle antibodies, and antismooth muscle antibodies. Immunoglobulin fractions and complement were normal for age in all of the patients.
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PMID:Peripheral lymphocyte subsets and other immune aspects in Rett syndrome. 1051 87

Because of the recent identification of several mutations of methyl-CpG-binding protein 2 (MECP2) in patients with Rett syndrome (RTT), a patient with suspected RTT from an autism clinic was screened for mutations. She was found to have a novel heterozygous nonsense mutation, 129C>T (Q19X), which leads to the most severely truncated MECP2 protein reported to date. Sequencing of parental DNA revealed the mutation was de novo. The patient was not affected with microcephaly or hyperventilation, but had other features of Rett syndrome including severe mental retardation and symptoms of autistic disorder. Moderately skewed X-chromosome inactivation (XCI) may have contributed to her relatively mild phenotype.
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PMID:Novel de novo nonsense mutation of MECP2 in a patient with Rett syndrome. 1073 89

Autistic Disorder was described by Leo Kanner in 1943. Since that time not only the name of this disorder (initially early infantile autism) has changed but also it's relation to other disorders. DSM-IV includes autism together with Rett's Disorder, Childhood Disintegrative Disorder, Asperger's Disorder and Pervasive Developmental Disorder Not Otherwise Specified into one category: Pervasive Developmental Disorders. The definition and contents of Pervasive Developmental Disorders raise many controversies. Differentiation between particular disorders within this category is also difficult. This paper discusses some of these problems.
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PMID:[Pervasive developmental disorders: controversies concerning the classification of autism]. 1105 83

Rett syndrome is a neurodevelopmental disorder affecting almost exclusively females. It affects approximately one in 15000 females and is characterized by a loss of purposeful hand use, autism, ataxia and seizure. The disorder is usually sporadic, but rare familial cases have also been reported. Recently it has been shown that familial cases are an X-linked dominant disorder and the disease locus maps to Xq28. A candidate gene called methyl-CpG-binding protein 2 was identified from the Xq28 region and was shown to contain mutations in about 77% of Rett syndrome patients. Since the encoded protein was previously shown to be a global transcriptional repressor, undesired expression of yet unidentified genes that are normally repressed is considered to be pathogenic in Rett syndrome.
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PMID:Molecular genetics of Rett syndrome. 1124 98

The diagnosis of Angelman syndrome (AS) can be confirmed by genetic laboratory in about 80% of cases. In 20%, the diagnosis remains clinical, but often there is uncertainty about the correctness of the clinical diagnosis and alternative diagnoses may be investigated. In evaluating individuals for AS in our center since 1989, we have encountered several mimicking conditions, and additional ones have been reported in the literature. Mimicking conditions can be grouped into the areas of chromosome, single gene, and symptom complex anomalies. Microdeletions or microduplications include chromosome regions 2,4,17, 22, and 15. Single gene conditions include methylene tetrahydrofolate reductase deficiency (MTHFR), Rett syndrome, alpha-thalassemia retardation syndrome (ATR-X), and Gurrieri syndrome. Symptom complexes include cerebral palsy, static encephalopathy, Lennox-Gastaut syndrome, autism spectrum disorder, pervasive developmental delay (PDD), and mitochondrial disorders. We present a review of these mimicking disorders to increase the awareness about conditions that can lead to an incorrect clinical diagnosis of AS.
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PMID:Angelman syndrome: mimicking conditions and phenotypes. 1175 74

In summary, autism genetics has moved from a time of identification of heritability and determination of risk of "lesser variants" or the "broader phenotype" in relatives to a phase where some cases of autism have a definite basis such as maternally inherited duplications of 15q11-q13, identification of mutations causing AS, Rett syndrome, and FRAXA. The first phase of genome-wide screens has not revealed definitive linkage, but as samples are enlarged and meta-analyses performed, the strongest linkage findings are likely to yield susceptibility variants once fine mapping proceeds. Recent statistical and molecular genetic analysis methods make the additional work feasible. However, frustrating it may be to be in this phase of the research, it is an essential part of the process of moving from identification of heritability in autism to understanding of the disorder in a way that may permit improved treatment in the future. If there is an advantage to autism being a complex rather than monogenic disorder, it is that the nature of multiplicative or interacting genetic risk is that prevention or treatment directed to any of the identified genetic risks may be sufficient to break a chain of pathophysiology. More genes increase the chance that one or more will have implications for treatment development sooner.
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PMID:Genetics of autism. 1135 2

Autistic disorder is a pervasive developmental disorder considered to have a multigenic origin. Mental retardation is present in 75% of autistic patients. Autistic features are found in Rett syndrome, a neurological disorder affecting girls and associated with severe mental retardation. Recently, the gene responsible for the Rett syndrome, methyl CpG-binding protein (MECP2) gene, was identified on the X chromosome by a candidate gene strategy. Mutations in this gene were also observed in some mentally retarded males. In this study we tested MECP2 as a candidate gene in autistic disorder by a DGGE analysis of its coding region and intron-exon boundaries. Among 59 autistic patients, 42 males and 17 females, mentally retarded or not, no mutations or polymorphisms were present in the MECP2 gene. Taking into account the size of our sample, we conclude that MECP2 coding sequence mutations are not an important factor (less than 5% of cases) in the aetiology of autistic disorder.
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PMID:No mutations in the coding region of the Rett syndrome gene MECP2 in 59 autistic patients. 1146 49


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