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

A group of 12 children clinically presenting with hypotonia, intractable epilepsy, autism, and developmental delay, who did not fall into previously described categories of mitochondrial encephalomyopathy, were evaluated for mitochondrial respiratory enzyme activity levels, mitochondrial DNA, and mitochondrial structural abnormalities. Reduced levels in specific respiratory activities were found solely in enzymes with subunits encoded by mitochondrial DNA in seven of eight biopsied skeletal muscle specimens evaluated. Five cases exhibited increased levels of large-scale mitochondrial DNA deletions, whereas pathogenic point mutations previously described in association with mitochondrial encephalomyopathies were not found. Mitochondrial structural abnormalities were present in three of four patients examined. Our findings suggest that mitochondrial dysfunction, including extensive abnormalities in specific enzyme activities, mitochondrial structure, and mitochondrial DNA integrity, may be present in children with a clinical constellation including hypotonia, epileptic seizures, autism, and developmental delay. The acronym HEADD is presented here to facilitate pursuit of mitochondrial defects in patients with this clinical constellation after other causes have been excluded.
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PMID:Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. 1217 64

Piccolo belongs to a family of presynaptic cytoskeletal proteins likely to be involved in the assembly and function of presynaptic active zones as sites of neurotransmitter release. Given that abnormalities in the formation of synaptic junctions are thought to contribute to cognitive dysfunction during brain development, we have analyzed and compared the gene structure of the Piccolo gene, PCLO, from humans and mice and determined their chromosomal localization. A comparison of the deduced amino acid sequence of cDNA clones encoding Piccolo from human, mouse, rat and chicken reveals the presence of distinct homology domains. Only subsets of these are also present in the structurally related active zone protein Bassoon indicating that Piccolo and Bassoon perform related but distinct functions at active zones. Characterization of the PCLO gene reveals the presence of 25 coding exons spread over 380kb of genomic DNA. The human PCLO gene maps to 7q11.23-q21.3, a region of chromosome 7 implicated as a linkage site for autism and Williams Syndrome suggesting that alterations in the expression of Piccolo or the PCLO gene could contribute to developmental disabilities and mental retardation.
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PMID:Gene structure and genetic localization of the PCLO gene encoding the presynaptic active zone protein Piccolo. 1217 52

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 methyl-CpG binding protein 2 (MeCP2) gene has recently been identified as the gene responsible for Rett syndrome (RS), a pervasive developmental disorder considered by many to be one of the autism spectrum disorders. Most female patients with MeCP2 mutations exhibit the classic features of RS, including autistic behaviors. Most male patients with MeCP2 mutations exhibit moderate to severe developmental delay/mental retardation. Ninety nine patients from the South Carolina autism project (SCAP) were screened for MeCP2 mutations, including all 41 female patients from whom DNA samples were available plus the 58 male patients with the lowest scores on standard IQ tests and/or the Vineland Adaptive Behavior Scale. No pathogenic mutations were observed in these patients. One patient had the C582T variant, previously reported in the unaffected father of an RS patient. Two other patients had single nucleotide polymorphisms in the 3' UTR of the gene, G1470A and C1516G. These variants were seen in 12/82 and 1/178 phenotypically normal male controls, respectively. The findings from this and other studies suggest that mutations in the coding sequence of the MeCP2 gene are not a significant etiological factor in autism.
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PMID:Absence of MeCP2 mutations in patients from the South Carolina autism project. 1255 43

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
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PMID:Human chromosome 7: DNA sequence and biology. 1269 Feb 5

The clinical significance of an interstitial duplication of (15)(q11-q13) remains unclear and controversial. The reported phenotypes vary widely and appear to be influenced by the parent of origin of the duplication. Aside from cases of dup(15) reported with autism, the behavioral phenotype of individuals with dup(15) has not been described. We present three families, two with intrachromosomal duplication (15)(q11-q13) ascertained because of developmental delay in a relative. Two families show clear evidence of multigenerational maternal inheritance. The individuals discussed in this paper have minor anomalies and developmental delays. In addition, we describe a behavioral phenotype which often includes attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder. Responses to medications used to manage these behaviors are also described, including a positive response to methylphenidate and a poor response to fluoxetine. The duplication in each presenting individual, and available family members, was investigated utilizing cytogenetic and molecular techniques including high resolution cytogenetics, fluorescence in situ hybridization (FISH), DNA methylation studies, and quantitative fluorescence PCR. High resolution cytogenetic techniques alone missed some cases, demonstrating the need to confirm results with other methods.
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PMID:Genetic and clinical characterization of patients with an interstitial duplication 15q11-q13, emphasizing behavioral phenotype and response to treatment. 1274 48

Several methods have been developed for the immortalization of B lymphocytes by Epstein-Barr virus (EBV). We developed an efficient method which reduces the time from culture initiation to immortalization and cryopreservation. Two infections of EBV to lymphocytes, and the use of phorbol ester-induced EBV stock significantly improved immortalization efficiency and reduced the time between initiation and immortalization and cryopreservation. The resulting cell bank was used to produce DNA for genetic studies focusing on the genes involved in immune and autistic disorders.
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PMID:An efficient method for the rapid establishment of Epstein-Barr virus immortalization of human B lymphocytes. 1554 76

We encountered seven children with symptomatic congenital cytomegalovirus (CMV) infection from 1988 to 1995, of whom two (28.6%) developed typical autistic disorder. Case 1: A boy born at 38 weeks' gestation with a birth weight of 3164 g showed generalized petechiae, hepatosplenomegaly, and positive serum CMV-specific IgM antibodies. He was profoundly deaf, mentally retarded, and exhibited a lack of eye contact, stereotyped repetitive play, and hyperactivity. Case 2: A boy delivered at 39 weeks gestation with a birthweight of 2912 g showed non-progressive dilatation of the lateral ventricles observed postnatally. CMV-specific IgM antibodies were positive and CMV-DNA in the urine was confirmed by PCR. The boy was mentally retarded but not deaf. He showed no interest in people and delayed speech development. Subependymal cysts were detected by cranial ultrasound after birth in both patients. This is the first report describing subependymal cysts and the later development of AD. Cranial magnetic resonance imaging revealed an abnormal intensity area in the periventricular white matter suggestive of disturbed myelination; however, no migration disorders were found in our patients. These findings suggest that the timing of injury to the developing brain by CMV may be in the third trimester in some patients with autistic disorder.
J Autism Dev Disord 2003 Aug
PMID:Possible association between congenital cytomegalovirus infection and autistic disorder. 1295 25

Australian research in psychiatric genetics covers molecular genetic studies of depression, anxiety, alcohol dependence, Alzheimer's disease, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. For each disorder, a variety of clinical cohorts have been recruited including affected sib pair families, trios, case/controls, and twins from a large population-based twin registry. These studies are taking place both independently and in collaboration with international groups. Microarray studies now complement DNA investigations, while animal models are in development. An Australian government genome facility provides a high throughput genotyping and mutation detection service to the Australian scientific community, enhancing the contribution of Australian psychiatric genetics groups to gene discovery.
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PMID:Psychiatric genetics in Australia. 1296 Jul 44

Rett syndrome is caused by mutation in MECP2, a gene located on Xq28 and subject to X-inactivation. MECP2 encodes methyl CpG-binding protein 2, a widely expressed transcriptional repressor of methylated DNA. Mutations in MECP2 are primarily de novo events in the male germ line and thus lead to an excess of affected females. Here we report the identification of a unique 47,XXX girl with relatively mild atypical Rett syndrome leading initially to a diagnosis of infantile autism with regression. Mutation analysis of the MECP2 gene identified a de novo MECP2 mutation, L100V. Examination of a panel of X-linked microsatellite markers indicated that her supernumerary X chromosome is maternally derived. X-inactivation patterns were determined by analysis of methylation of the androgen receptor locus, and indicated preferential inactivation of her paternal allele. The parental origin of her MECP2 mutation could not be determined because she was uninformative for intronic polymorphisms flanking her mutation. This is the first reported case of sex chromosome trisomy and MECP2 mutation in a female, and it illustrates the importance of allele dosage on the severity of Rett syndrome phenotype.
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PMID:Rett syndrome in a 47,XXX patient with a de novo MECP2 mutation. 1296 22


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