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

Since autism was first described by Leo Kanner the view on its etiology and pathogenesis has been changing. Recently there are more data on genetic and neurobiological background of autism. At the beginning it was noticed that autism appeared more frequently among boys, in population studies it was found that autism appeared more frequently among siblings, mostly among monozygotic twins. Many disorders like Tourett syndrome and tuberous sclerosis were reported in connection with autism. Recently research is focused mostly on chromosome abnormalities: chromosome 15 (locus 15q11-13), chromosome 7 (locus 7q), chromosome 16 (locus 16p) and gens of particular receptors (GABRB3, UBE3A/E6-AP, 5-HTT). These abnormalities may also be one of the causes of autism.
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PMID:[Genetic studies in autistic disorders]. 1105 82

To assess the prevalence of macrocephaly (head circumference > or = 1.88 standard deviations above normative data for age and sex or > 97th centile) in autism and other pervasive developmental disorders, 41 children with autism, and a comparison group of 21 children with tuberous sclerosis complex (TSC) or an unspecified seizure disorder were studied. Familiality of head circumference was also assessed from measurements of 133 first-degree relatives. Significantly higher rates of macrocephaly were found in probands with autism (12.2%) and their first-degree relatives (15.5%) when compared against a published normative sample. The incidence of macrocephaly in the comparison group of probands with TSC and seizure disorder (9.5%) and their first-degree relatives (8.3%) was higher than normative data as well, although the relation between macrocephaly and autism was more pronounced. Head circumference and extreme scores reflecting macrocephaly were moderately heritable in the present sample (H2 = 0.47). The increased prevalence of macrocephaly in relatives of children with autism compared with control children suggests that this characteristic may be a familial risk factor in the pathogenesis of autism.
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PMID:Macrocephaly in autism and other pervasive developmental disorders. 1110 44

We have sequenced 1949 kb from the terminal Giemsa light band of human chromosome 16p, enabling us to fully annotate the region extending from the telomeric repeats to the previously published tuberous sclerosis disease 2 (TSC2) and polycystic kidney disease 1 (PKD1) genes. This region can be subdivided into two GC-rich, Alu-rich domains and one GC-rich, Alu-poor domain. The entire region is extremely gene rich, containing 100 confirmed genes and 20 predicted genes. Many of the genes encode widely expressed proteins orchestrating basic cellular processes (e.g. DNA recombination, repair, transcription, RNA processing, signal transduction, intracellular signalling and mRNA translation). Others, such as the alpha globin genes (HBA1 and HBA2), PDIP and BAIAP3, are specialized tissue-restricted genes. Some of the genes have been previously implicated in the pathophysiology of important human genetic diseases (e.g. asthma, cataracts and the ATR-16 syndrome). Others are known disease genes for alpha thalassaemia, adult polycystic kidney disease and tuberous sclerosis. There is also linkage evidence for bipolar affective disorder, epilepsy and autism in this region. Sixty-three chromosomal deletions reported here and elsewhere allow us to interpret the results of removing progressively larger numbers of genes from this well defined human telomeric region.
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PMID:Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. 1115 97

The paper provides clinical and catamnestic descriptions of 240 children with infantile autism; 160 with atypical autism (of them 100 had schizophrenic attacks, 60 presented with mental retardation concurrent with atypical autism (in phenylketonuria, tuberose sclerosis, Down syndrome, Martin-Bell syndrome), 20 with Asperger's syndrome, 60 with Rett's syndrome, 20 with psychogenic paraautism according the Nissen classification. The similarity of autism-like disorders and atypical autism was considered. Syndromal verifications in accordance with ICD-10 (1994) and ICD-10 (1999) in Russian versions and clinical nosological verifications adopted in Russia were studied in all the examinees. New approaches to treating patients with autistic disorders were developed.
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PMID:[Current approaches to the problem of autism in childhood]. 1152 31

Children with autism have an increased risk for obstetric complications but it is not known whether these are of primary aetiological significance. It is also unclear whether obstetric complications play a secondary role in shaping phenotypic expression in individuals at genetic risk for autism. We investigated this question by studying the role of obstetric complications in determining phenotypic manifestations in tuberous sclerosis, a single gene disorder frequently associated with autism spectrum disorders. Obstetric histories of 43 children with non-familial TS and 40 unaffected siblings were obtained using a structured parent interview. ADI-R, ADOS-G and IQ evaluations were undertaken. Children with TS experienced more obstetric complications than their unaffected siblings, but these were related to mild rather than severe adversities. No differences in obstetric complications were found in children with and without autism spectrum disorders and there was no positive correlation between obstetric adversities and severity of autism spectrum disorders or intellectual impairments.
Autism 2001 Sep
PMID:Pervasive developmental disorder and obstetric complications in children and adolescents with tuberous sclerosis. 1170 84

Autistic disorder is a behavioural syndrome beginning before the age of 3 years and lasting over the whole lifetime. It is characterised by impaired communication, impaired social interactions, and repetitive interests and behaviour. The prevalence is about 7/10,000 taking a restrictive definition and more than 1/500 with a broader definition, including all the pervasive developmental disorders. The importance of genetic factors has been highlighted by epidemiological studies showing that autistic disorder is one of the most genetic neuropsychiatric diseases. The relative risk of first relatives is about 100-fold higher than the risk in the normal population and the concordance in monozygotic twin is about 60%. Different strategies have been applied on the track of susceptibility genes. The systematic search of linked loci led to contradictory results, in part due to the heterogeneity of the clinical definitions, to the differences in the DNA markers, and to the different methods of analysis used. An oversimplification of the inferred model is probably also cause of our disappointment. More work is necessary to give a clearer picture. One region emerges more frequently: the long arm of chromosome 7. Several candidate genes have been studied and some gave indications of association: the Reelin gene and the Wnt2 gene. Cytogenetical abnormalities are frequent at 15q11-13, the region of the Angelman and Prader-Willi syndrome. Imprinting plays an important role in this region, no candidate gene has been identified in autism. Biochemical abnormalities have been found in the serotonin system. Association and linkage studies gave no consistent results with some serotonin receptors and in the transporter, although it seems interesting to go further in the biochemical characterisation of the serotonin transporter activity, particularly in platelets, easily accessible. Two monogenic diseases have been associated with autistic disorder: tuberous sclerosis and fragile X. A better knowledge of the pathophysiology of these disorders can help to understand autism. Different other candidate genes have been tested, positive results await replications in other samples. Animal models have been developed, generally by knocking out the different candidate genes. Behaviour studies have mainly focused on anxiety and learning paradigms. Another group of models results from surgical or toxic lesions of candidate regions in the brain, in general during development. The tools to analyse these animals are not yet standardised, and an important effort needs to be undertaken.
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PMID:Molecular genetics and animal models in autistic disorder. 1182 43

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by seizures, mental retardation, autism, and tumors of multiple organs. Renal disease in TSC includes angiomyolipomas, cysts, and renal cell carcinomas. It is known that somatic mutations in the von Hippel Lindau (VHL) tumor suppressor gene occur in most clear cell renal carcinomas. To determine whether TSC-associated clear cell carcinomas also contain VHL mutations, we analyzed six tumors for loss of heterozygosity in the VHL gene region of chromosome 3p and for mutations in the VHL gene. Four of the patients were women between the ages of 34 and 68 years, and two were males under the age of 21 years. The loss of heterozygosity analysis was performed using polymorphic microsatellite markers, and the mutational analysis was performed using direct sequencing. Chromosome 3p loss of heterozygosity was not detected, and no VHL mutations were identified. These findings suggest that mutations in the TSC1 and TSC2 genes lead to clear cell renal carcinogenesis via an alternate pathway not involving VHL mutations.
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PMID:Mutational analysis of the von hippel lindau gene in clear cell renal carcinomas from tuberous sclerosis complex patients. 1190 37

Tuberous sclerosis complex is characterized by hamartomatous lesions involving skin, brain, kidneys, eyes and heart. Pathologically, tuberous sclerosis is a disorder of cell migration, proliferation and differentiation. Cell lineage and cell migration disorders in the developing cortex of tuberous sclerosis complex patients might produce very different neurological phenotypes including epilepsy, cognitive impairment and autism. Cortical tubers constitute the hallmark of the disease and are pathognomonic of cerebral tuberous sclerosis. Epilepsy is the most common neurological feature, occurring in 96% of patients. Seizures often begin in the first months of life and are frequently severe and intractable. The treatment of seizures has recently benefited from the advent of the new anti-epileptic drugs. Selected drug-resistant patients with tuberous sclerosis complex could be considered for surgical treatment. Clear localization of the most active epileptogenic focus and the zone of the cortical abnormality may lead to tuberectomy and improved seizure control in selective drug-resistant patients. The finding of multiple areas of cerebral involvement should not automatically preclude epilepsy surgery in a child with intractable seizures and a well defined seizure origin.
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PMID:Tuberous sclerosis complex: a review of neurological aspects. 1199 52

Tuberous sclerosis is one of the few established medical causes of autism spectrum disorder and is a unique neurogenetic model for testing theories about the brain basis of the syndrome. We conducted a retrospective case study of the neuro-epileptic risk factors predisposing to autism spectrum disorder in individuals with tuberous sclerosis to test current neurobiological theories of autism spectrum disorder. We found that an autism spectrum disorder diagnosis was associated with the presence of cortical tubers in the temporal but not other lobes of the brain. Indeed, the presence of tubers in the temporal lobes appeared to be a necessary but not sufficient risk factor for the development of an autism spectrum disorder. However, contrary to the predictions of some theories, the location of tubers in specific regions of the temporal lobe, such as the superior temporal gyrus or the right temporal lobe, did not determine which individuals with temporal lobe tubers developed an autism spectrum disorder. Instead, outcome was associated with various indices of epileptic activity including evidence of temporal lobe epileptiform discharges on EEG, the age to onset of seizures in the first 3 years of life and a history of infantile spasms. The results indicated that individuals with tuberous sclerosis are at very high risk of developing an autism spectrum disorder when temporal lobe tubers are present and associated with temporal lobe epileptiform discharges and early-onset, persistent spasm-like seizures. These risk markers constitute useful clinical indicators of prognosis, but further research is required to identify the neurobiological mechanisms responsible for their association with outcome. Most especially, it will be important to test whether, as the findings suggest, there is a critical early stage of brain maturation during which temporal lobe epilepsy perturbs the development of brain systems that underpin 'social intelligence' and possibly other cognitive skills, thereby inducing an autism spectrum disorder.
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PMID:Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. 1202 13

Tuberous sclerosis complex (TSC) is an autosomal dominant tumor predisposition syndrome characterized by benign proliferations (hamartomas). In the brain, individuals with TSC develop autism, mental retardation and seizures associated with focal cortical dysplasias, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). We hypothesize that dysregulated astrocyte function due to mutations in the tumor suppressor genes, TSC1 and TSC2, may contribute to the pathogenesis of these brain abnormalities. In this report, we demonstrate that mice heterozygous for a targeted defect in either the Tsc1 or Tsc2 genes(Tsc1+/- and Tsc2+/- mice) exhibit a 1.5-fold increase in the number of astrocytes in vivo. Whereas increased astrocyte numbers in vivo were suggestive of a proliferative advantage, Tsc2+/- primary astrocyte cultures did not show a cell-autonomous growth advantage, anchorage-independent growth, increased saturation density, or increased fluid-phase endocytosis compared to wild type astrocytes. Tsc2 null mouse embryonic fibroblasts (MEFs) however, did exhibit increased saturation density compared to Tsc2 wild type controls. In both Tsc2+/- astrocytes and Tsc2 null mouse embryonic fibroblasts, p27-Kip1 expression was decreased compared to wild type cells, and was reversed by tuberin re-expression in Tsc2-/- MEFs. In contrast, no change in endocytosis was observed upon tuberin re-expression in Tsc2-/- MEFs. Collectively, these results suggest Tsc heterozygosity may provide a non-cell-autonomous growth advantage for astrocytes that may involve p27-Kip1 expression.
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PMID:Heterozygosity for the tuberous sclerosis complex (TSC) gene products results in increased astrocyte numbers and decreased p27-Kip1 expression in TSC2+/- cells. 1203 87


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