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

Epidemiological data and family studies in autism show that there is a genetic susceptibility factor in the aetiology of this syndrome. We carried out an association study in infantile autism. Two markers of the homeogene EN2 involved in cerebellar development were tested in a population of 100 autistic children and in a population of 100 control children. With the MP4 probe showing a PvuII polymorphism, significant differences in the allele frequencies between the two populations were found (chi 2 = 7.99, df = 1, p < 0.01). With the MP5 probe showing an SstI polymorphism, no difference appeared (chi 2 = 1.17, not significant). Several clinical examinations allowed us to characterise the autistic children. Most of them had high scores for autistic behaviour and language disorders but low scores for neurological syndromes. Two children had a significant family history and six children had confirmed syndromes or diseases of genetic origin. Discriminant analysis between clinical and molecular data did not give significant results. These preliminary results must be supported by further analyses of this gene and by studies of its potential involvement in the pathophysiology of the autistic syndrome.
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PMID:Association study with two markers of a human homeogene in infantile autism. 764 54

The etiology of autism is complex, and in most cases the underlying pathologic mechanisms are unknown. Autism is a hetereogeneous disorder, diagnosed subjectively on the basis of a large number of criteria. Recent research has investigated genetics, in utero insults and brain function as well as neurochemical and immunological factors. On the basis of family and twin studies, there appears to be a genetic basis for a wide "autistic syndrome." About a quarter of cases of autism are associated with genetic disorders such as fragile X syndrome or with infectious diseases such as congenital rubella. Genetic studies have shown an association between autism markers of brain development such as 3 markers of the c-Harvey-ros oncogene and the homeobox gene EN2. In some cases, autism is associated with insults early in gestation, including thalidomide embryopathy. Autism may arise from abnormal central nervous system functioning, since most autistic patients have indications of brain dysfunction, and about half of them have abnormal electroencephalograms. Similarly, the pattern of evoked response potentials and conduction time is altered in autistic children. There is substantial evidence from neuroimaging studies that dysfunctions in the cerebellum and possibly the temporal lobe and association cortex occur in autistic symptoms. Neurochemical studies have investigated the role of serotonin, epinephrine and norepinephrine, since levels of these neurotransmitters are altered in autism, although other hypotheses implicate overactive brain opioid systems and changes in oxytocin neurotransmission. Autoimmunity may also play a role; antibodies against myelin basic protein are often found in children with autism, who also have increased eosinophil and basophil response to IgE-mediated reactions. In summary, the prevailing view is that autism is caused by a pathophysiologic process arising from the interaction of an early environmental insult and a genetic predisposition.
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PMID:Etiology of infantile autism: a review of recent advances in genetic and neurobiological research. 1021 50

Human chromosome 7q31 contains putative susceptibility loci for autism (AUTS1) and speech and language disorder (SPCH1). We report here the identification and characterization of a novel gene encoding cortactin-binding protein-2 (CORTBP2), which is located 45 kb telomeric to the cystic fibrosis transmembrane conductance regulator gene (CFTR) at 7q31.3. The full-length (5975-bp) gene was isolated and found to be composed of 23 exons encompassing 170 kb of DNA. In addition to being a positional candidate for AUTS1, CORTBP2 was expressed at highest levels in the brain, as shown by northern blot analysis. Subsequent mutation analysis of CORTBP2 in 90 autistic patients identified two polymorphisms, including a leucine to valine change caused by a T to G substitution in exon 15. However, comparison of allele frequencies between autistic and control populations (n=96) showed no significant difference, suggesting that this variant is not a susceptibility factor for autism.
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PMID:Identification of the human cortactin-binding protein-2 gene from the autism candidate region at 7q31. 1170 66

The FOXP2 gene, located on human 7q31 (at the SPCH1 locus), encodes a transcription factor containing a polyglutamine tract and a forkhead domain. FOXP2 is mutated in a severe monogenic form of speech and language impairment, segregating within a single large pedigree, and is also disrupted by a translocation in an isolated case. Several studies of autistic disorder have demonstrated linkage to a similar region of 7q (the AUTS1 locus), leading to the proposal that a single genetic factor on 7q31 contributes to both autism and language disorders. In the present study, we directly evaluate the impact of the FOXP2 gene with regard to both complex language impairments and autism, through use of association and mutation screening analyses. We conclude that coding-region variants in FOXP2 do not underlie the AUTS1 linkage and that the gene is unlikely to play a role in autism or more common forms of language impairment.
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PMID:FOXP2 is not a major susceptibility gene for autism or specific language impairment. 1189 22

Genetic studies indicate that chromosome 7q is likely to contain an autism susceptibility locus (AUTS1). We have followed a positional candidate gene approach to identify the relevant gene and report the analysis of four adjacent genes localised to a 800 kb region in 7q32 that contains an imprinted domain: PEG1/MEST, COPG2, CPA1 and CPA5-a previously uncharacterised member of the carboxypeptidase gene family. Screening these genes for DNA changes and association analysis using intragenic single nucleotide polymorphisms (SNPs) provided no evidence for an etiological role in IMGSAC families. We also searched for imprinting mutations potentially implicated in autism: analysis of both DNA methylation and replication timing indicated a normal imprinting regulation of the PEG1/COPG2 domain in blood lymphocytes of all patients tested. The analysis of these four genes strongly suggests that they do not play a major role in autism aetiology, and delineates our strategy to screen additional candidate genes in the AUTS1 locus.
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PMID:Mutation screening and imprinting analysis of four candidate genes for autism in the 7q32 region. 1192 Jan 56

To identify genetic loci for autism-spectrum disorders, we have performed a two-stage genomewide scan in 38 Finnish families. The detailed clinical examination of all family members revealed infantile autism, but also Asperger syndrome (AS) and developmental dysphasia, in the same set of families. The most significant evidence for linkage was found on chromosome 3q25-27, with a maximum two-point LOD score of 4.31 (Z(max )(dom)) for D3S3037, using infantile autism and AS as an affection status. Six markers flanking over a 5-cM region on 3q gave Z(max dom) >3, and a maximum parametric multipoint LOD score (MLS) of 4.81 was obtained in the vicinity of D3S3715 and D3S3037. Association, linkage disequilibrium, and haplotype analyses provided some evidence for shared ancestor alleles on this chromosomal region among affected individuals, especially in the regional subisolate. Additional potential susceptibility loci with two-point LOD scores >2 were observed on chromosomes 1q21-22 and 7q. The region on 1q21-22 overlaps with the previously reported candidate region for infantile autism and schizophrenia, whereas the region on chromosome 7q provided evidence for linkage 58 cM distally from the previously described autism susceptibility locus (AUTS1).
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PMID:A genomewide screen for autism-spectrum disorders: evidence for a major susceptibility locus on chromosome 3q25-27. 1219 42

Previous genetic and cytogenetic studies provide evidence that points to one or more autism susceptibility genes residing on chromosome 7q (AUTS1, 115-149 cM on the Marshfield map). However, further localization using linkage analysis has proven difficult. To overcome this problem, we examined the Collaborative Linkage Study of Autism (CLSA) data-set to identify only the families potentially linked to chromosome 7. Out of 94, 47 families were identified and 17 markers were used to generate chromosomal haplotypes. We performed recombination breakpoint analysis to determine if any portion of the chromosome was predominately shared across families. The most commonly shared region spanned a 6 cM interval between D7S501 and D7S2847. Additional markers at 1 cM intervals within this region were genotyped and association and recombination breakpoint analysis was again performed. Although no significant allelic association was found, the recombination breakpoint data points to a shared region between D7S496-D7S2418 (120-123 cM) encompassing about 4.5 Mb of genomic DNA containing over 50 genes.
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PMID:Defining the autism minimum candidate gene region on chromosome 7. 1255 42

The recent identification of some of the components involved in regulated and constitutive exocytotic pathways has yielded important insights into the mechanisms of membrane trafficking and vesicle secretion. To understand precisely the molecular events taking place during vesicle exocytosis, we must identify all of the proteins implicated in these pathways. In this paper we describe the full-length cloning and characterization of human CADPS and CADPS2, two new homologs of the mouse Cadps protein involved in large dense-core vesicle (LDCV)-regulated exocytosis. We show that these two genes have disparate RNA expression patterns, with CADPS restricted to neural and endocrine tissues and CADPS2 expressed ubiquitously. We also identify a C2 domain, a known protein motif involved in calcium and phospholipid interactions, in both CADPS and CADPS2. We propose that CADPS functions as a calcium sensor in regulated exocytosis, whereas CADPS2 acts as a calcium sensor in constitutive vesicle trafficking and secretion. CADPS and CADPS2 were determined to span 475 kb and 561 kb on human chromosomes 3p21.1 and 7q31.3, respectively. The q31-q34 of human chromosome 7 has recently been identified to contain a putative susceptibility locus for autism (AUTS1). The function, expression profile, and location of CADPS2 make it a candidate gene for autism, and thus we conducted mutation screening for all 28 exons in 90 unrelated autistic individuals. We identified several nucleotide substitutions, including only one that would affect the amino acid sequence. No disease-specific variants were identified.
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PMID:Cloning and characterization of human CADPS and CADPS2, new members of the Ca2+-dependent activator for secretion protein family. 1265 12

Recent molecular studies on autism and related disorders have supported a multilocus etiology for the disease spectrum. To maximize genetic and cultural homogeneity, we have focused our molecular studies to families originating from a subisolate of Central Finland. Genealogical studies enabled the identification of a megapedigree comprising of 12 core families with autism and Asperger syndrome (AS). We analyzed two chromosomal regions on Iq and 3q showing highest lod scores in our genome-wide scan, as well as the AUTS1 locus on chromosome 7q. For markers on 3q25-27, more significant association was observed in families from subisolate compared to families from the rest of Finland. In contrast, no clear evidence for association on AUTS1 locus was obtained. The wide interval showing association, in particular, on chromosome 3q suggests a locus for autism spectrum of disorders on this chromosomal region.
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PMID:Evidence for allelic association on chromosome 3q25-27 in families with autism spectrum disorders originating from a subisolate of Finland. 1451 38

Genetic studies indicate that chromosome 7q is likely to contain an autism susceptibility locus (AUTS1). We have followed a positional candidate gene approach to identify relevant gene(s) and report here the analysis of reelin (RELN), a gene located under our peak of linkage. Screening RELN for DNA changes identified novel missense variants absent in a large control group; however, the low frequency of these mutations does not explain the relatively strong linkage results on 7q. Furthermore, analysis of a previously reported triplet repeat polymorphism and intragenic single nucleotide polymorphisms, using the transmission disequilibrium test, provided no evidence for association with autism in IMGSAC and German singleton families. The analysis of RELN suggests that it probably does not play a major role in autism aetiology, although further analysis of several missense mutations is warranted in additional affected individuals.
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PMID:Analysis of reelin as a candidate gene for autism. 1451 39


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