Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A region on chromosome 17 has recently been highlighted as linked to autism (MIM[209850]) in multiple studies and evidence has accumulated suggesting that male-only families (those families that have produced only affected males) provide the major contribution to linkage at this locus. In an attempt to comprehensively test for association of common variants to autism within the region on chromosome 17 defined in Stone et al. (Stone, J.L., Merriman, B., Cantor, R.M., Yonan, A.L., Gilliam, T.C., Geschwind, D.H. and Nelson, S.F. (2004) Evidence for sex-specific risk alleles in autism spectrum disorder. Am. J. Hum. Genet., 75, 1117-1123), a dense panel of single nucleotide polymorphisms (SNPs) was selected across the linkage peak and analyzed in a trio-based study design. SNPs were genotyped in 219 independent trios at an average intermarker distance of 6.1 kb across the 13.7 Mb interval. This provided ~80% coverage of common HapMap variation present in Caucasians, testing exonic, intronic, promoter and intergenic regions, as knowledge of important functional regions within the genome is currently limited. In this comprehensive association study of a linkage region in autism, no single SNP or haplotype association was sufficient to account for the initial linkage signal. Nominally significant single SNP and/or haplotype-based association results were detected in 15 genes, of which, MYO1D, ACCN1 and LASP1 stand out as genes with autism risk alleles requiring further study, with potential GRRs in the range of 1.34-2.29.
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PMID:High density SNP association study of a major autism linkage region on chromosome 17. 1737 94

Myosin-1d is a monomeric actin-based motor found in a wide range of tissues, but highly expressed in the nervous system. Previous microarray studies suggest that myosin-1d is found in oligodendrocytes where transcripts are upregulated during the maturation of these cells. Myosin-1d was also identified as a component of myelin-containing subcellular fractions in proteomic studies and mutations in MYO1D have been linked to autism. Despite the potential implications of these previous studies, there is little information on the expression and localization of myosin-1d in the developing nervous system. Therefore, we analyzed myosin-1d expression patterns in the peripheral and central nervous systems during postnatal development. In mouse sciatic nerve, myosin-1d is expressed along the axon and in the ensheathing myelin compartment. Analysis of mouse cerebellum prior to myelination at day 3 reveals that myosin-1d is present in the Purkinje cell layer, granule cell layer, and region of the cerebellar nuclei. Upon the onset of myelination, myosin-1d enrichment expands along axonal tracts, while still present in the Purkinje and granule cell layers. However, myosin-1d was undetectable in oligodendrocyte progenitor cells at early and late time points. We also show that myosin-1d interacts and is co-expressed with aspartoacylase, an enzyme that plays a key role in fatty acid synthesis throughout the nervous system. Together, these studies provide a foundation for understanding the role of myosin-1d in neurodevelopment and neurological disorders.
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PMID:Expression and localization of myosin-1d in the developing nervous system. 2228 16

We describe a 32-year-old male patient diagnosed with high-functioning autism spectrum disorder carrying a de novo 196-kb interstitial deletion at chromosome 17q11.2. The deletion was detected by array CGH (180K Agilent) and confirmed by quantitative PCR on genomic DNA. The deleted region spans the entire PSMD11 and CDK5R1 genes and partially the MYO1D gene. The CDK5R1 gene encodes for a regulatory subunit of the cyclin-dependent kinase 5 responsible for its brain-specific activation. This gene has been previously associated with intellectual disability in humans. A reduction in CDK5R1 transcript was detected, consistent with the genomic deletion. Based on the functional role of CDK5R1, this gene appears as the best candidate to explain the clinical phenotype of our patient, whose neuropsychological profile has more resemblance with some of the higher brain function anomalies recently described in the CreER-p35 conditional knockout mouse model than previously described patients with intellectual disability.
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PMID:An Interstitial 17q11.2 de novo Deletion Involving the CDK5R1 Gene in a High-Functioning Autistic Patient. 3073 59