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

We report an 18-year-old female with a diagnosis of DSM-IV Autistic Disorder and moderate to severe mental retardation who was discovered to have a previously undescribed chromosomal abnormality 46, XX, duplication (4) p12-p13. We discuss her history and diagnosis, noting that the co-occurrence of her diagnoses have not previously been documented. The report adds to the literature supporting the argument that individuals with autistic spectrum disorders should be re-examined for chromosomal abnormalities.
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PMID:Case report: autistic disorder and chromosomal abnormality 46, XX duplication (4) p12-p13. 1120 7

In this report we describe the case of an 11-year-old male with autism and mental retardation, presenting a tetrasomy of chromosome 3q. Cytogenetic analysis showed a mosaic for an unbalanced karyotype consisting of mos46,XY,add(12)(p13.3)(56)/46,XY(45). FISH using WCP and subtelomeric probes identified the extra material on 12p to be an inverted duplication of the distal segment of chromosome 3q. Anomalies in chromosome 3q have not been previously described in association with autism, although association with psychomotor delays and behavior problems has been frequently reported and are here further discussed. This chromosomal 3q segment is therefore likely to include genes involved in specific neurodevelopment pathways, and further analysis of the region is warranted for the identification of the molecular alterations that lead to the autistic features described.
J Autism Dev Disord 2003 Apr
PMID:Partial tetrasomy of chromosome 3q and mosaicism in a child with autism. 1275 57

Autism is a neurodevelopmental disorder with high heritability and a likely complex genetic architecture. Much genetic evidence has accumulated in the last 20 years but no gene has been unequivocally identified as containing risk variants for autism. In this article we review the past and present literature on neuro-pathological, genetic linkage, genetic association, and gene expression studies in this disorder. We sought convergent evidence to support particular genes or chromosomal regions that might be likely to contain risk DNA variants. The convergent evidence from these studies supports the current hypotheses that there are multiple genetic loci predisposing to autism, and that genes involved in neurodevelopment are especially important for future genetic studies. Convergent evidence suggests the chromosome regions 7q21.2-q36.2, 16p12.1-p13.3, 6q14.3-q23.2, 2q24.1-q33.1, 17q11.1-q21.2, 1q21-q44 and 3q21.3-q29, are likely to contain risk genes for autism. Taken together with results from neuro-pathological studies, genes involved in brain development located at the above regions should be prioritized for future genetic research.
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PMID:A review of gene linkage, association and expression studies in autism and an assessment of convergent evidence. 1723 39

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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PMID:Mapping autism risk loci using genetic linkage and chromosomal rearrangements. 1732 80

Intellectual disability (ID) is a common disease. While the etiology remains incompletely understood, genetic defects are a major contributor, which include mutations in genes encoding zinc finger proteins. These proteins modulate gene expression via binding to DNA. Consistent with this knowledge, we report here the identification of mutations in the ZNF407 gene in ID/autistic patients. In our study of an ID patient with autism, a reciprocal translocation 46,XY,t(3;18)(p13;q22.3) was detected. By using FISH and long-range PCR approaches, we have precisely mapped the breakpoints associated with this translocation in a gene-free region in chromosome 3 and in the third intron of the ZNF407 gene in chromosome18. The latter reduces ZNF407 expression. Consistent with this observation, in our subsequent investigation of 105 ID/autism patients with similar clinical presentations, two missense mutations Y460C and P1195A were identified. These mutations cause non-conservative amino acid substitutions in the linker regions between individual finger structures. In line with the linker regions being critical for the integrity of zinc finger motifs, both mutations may result in loss of ZNF407 function. Taken together, we demonstrate that mutations in the ZNF407 gene contribute to the pathogenesis of a group of ID patients with autism.
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PMID:Balanced translocation t(3;18)(p13;q22.3) and points mutation in the ZNF407 gene detected in patients with both moderate non-syndromic intellectual disability and autism. 2319 52

Most balanced chromosomal aberrations are not associated with a clinical phenotype, however, in some patients they may disrupt gene structure. With the development of various next-generation sequencing techniques, fast and specific analyses of the breakpoint regions of chromosomal rearrangements are possible. Here, we report on a 19-year-old woman with a de novo balanced translocation t(2;8)(p13.2;q22.1) and a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features. By next-generation sequencing, we defined the breakpoints and found disruption of the exocyst complex component 6B (EXOC6B) gene in intron 1 on chromosome 2p13.2 involving two Alu elements with a homology of 81%. No gene was found at the respective breakpoint on chromosome 8. Expression analysis of the EXOC6B in blood lymphocytes and buccal smear revealed reduced expression in the patient in comparison with the control. Our findings in combination with one recently published case and one other patient listed in DECIPHER v5.1 indicate EXOC6B as a gene relevant for intellectual development and electrophysiological stability.
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PMID:Disruption of EXOC6B in a patient with developmental delay, epilepsy, and a de novo balanced t(2;8) translocation. 2342 42

Chromosomal copy-number variations (CNVs) are a class of genetic variants highly implicated in the aetiology of neurodevelopmental disorders, including intellectual disabilities (ID), schizophrenia and autism spectrum disorders (ASD). Yet the majority of adults with idiopathic ID presenting to psychiatric services have not been tested for CNVs. We undertook genome-wide chromosomal microarray analysis (CMA) of 202 adults with idiopathic ID recruited from community and in-patient ID psychiatry services across England. CNV pathogenicity was assessed using standard clinical diagnostic methods and participants underwent comprehensive medical and psychiatric phenotyping. We found an 11% yield of likely pathogenic CNVs (22/202). CNVs at recurrent loci, including the 15q11-q13 and 16p11.2-p13.11 regions were most frequently observed. We observed an increased frequency of 16p11.2 duplications compared with those reported in single-disorder cohorts. CNVs were also identified in genes known to effect neurodevelopment, namely NRXN1 and GRIN2B. Furthermore deletions at 2q13, 12q21.2-21.31 and 19q13.32, and duplications at 4p16.3, 13q32.3-33.3 and Xq24-25 were observed. Routine CMA in ID psychiatry could uncover ~11% new genetic diagnoses with potential implications for patient management. We advocate greater consideration of CMA in the assessment of adults with idiopathic ID presenting to psychiatry services.
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PMID:Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders. 2765 Sep 69

The GRIN2B (glutamate receptor, ionotropic, N-methyl-d-aspartate 2B) gene, located in the short arm of chromosome 12, encoding the NR2B subunit of the N-methyl-D-aspartate receptor, has recently been recognized to play an important role in corticogenesis and brain plasticity. Deletions in the short arm of chromosome 12 are rare. Hemizygous loss of function of the GRIN2B gene results in developmental delay, whereas gain of function leads to epilepsy, and infantile spasms in particular. In addition, GRIN2B variants have been associated with autism spectrum disorder and schizophrenia. Here the authors report a child with global developmental delay, autistic behavioural features, central hypotonia, dysmorphic features and isolated congenital anomalies of the fingers and toes, and a de novo heterozygous deletion in chromosome locus 12p13.2-p13.1, involving loss of several genes, including GRIN2B. This report and our review of the literature help clarify the distinct phenotypes associated with loss or gain of GRIN2B function.
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PMID:Chromosome 12p Deletion Spanning the GRIN2B Gene Presenting With a Neurodevelopmental Phenotype: A Case Report and Review of Literature. 2850 5

Epilepsy is a common episodic neurological disorder or condition characterized by recurrent epileptic seizures, and genetics seems to play a key role in its etiology. Early linkage studies have localized multiple loci that may harbor susceptibility genes to epilepsy, and mutational analyses have detected a number of mutations involved in both ion channel and nonion channel genes in patients with idiopathic epilepsy. Genome-wide studies of epilepsy have found copy number variants at 2q24.2-q24.3, 7q11.22, 15q11.2-q13.3, and 16p13.11-p13.2, some of which disrupt multiple genes, such as NRXN1, AUTS2, NLGN1, CNTNAP2, GRIN2A, PRRT2, NIPA2, and BMP5, implicated for neurodevelopmental disorders, including intellectual disability and autism. Unfortunately, only a few common genetic variants have been associated with epilepsy. Recent exome-sequencing studies have found some genetic mutations, most of which are located in nonion channel genes such as the LGI1, PRRT2, EFHC1, PRICKLE, RBFOX1, and DEPDC5 and in probands with rare forms of familial epilepsy, and some of these genes are involved with the neurodevelopment. Since epigenetics plays a role in neuronal function from embryogenesis and early brain development to tissue-specific gene expression, epigenetic regulation may contribute to the genetic mechanism of neurodevelopment through which a gene and the environment interacting with each other affect the development of epilepsy. This review focused on the analytic tools used to identify epilepsy and then provided a summary of recent linkage and association findings, indicating the existence of novel genes on several chromosomes for further understanding of the biology of epilepsy.
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PMID:Genetic and epigenetic mechanisms of epilepsy: a review. 2876 47

Chromosomal abnormalities are often identified in people with neurodevelopmental disorders including intellectual disability, autism, and epilepsy. Ring chromosomes, which usually involve gene copy number loss, are formed by fusion of subtelomeric or telomeric chromosomal regions. Some ring chromosomes, including ring 14, 17, and 20, are strongly associated with seizure disorders. We report an individual with a ring chromosome 17, r(17)(p13.3q25.3), with a terminal 17q25.3 deletion and no short arm copy number loss, and with a phenotype characterized by intellectual disability and drug-resistant epilepsy, including a propensity for nonconvulsive status epilepticus.
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PMID:Ring Chromosome 17 Not Involving the Miller-Dieker Region: A Case with Drug-Resistant Epilepsy. 2945 82


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