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)

Autism spectrum disorders (ASD) are highly heritable and genetically complex conditions. Although highly penetrant mutations in multiple genes have been identified, they account for the etiology of <1/3 of cases. There is also strong evidence for environmental contribution to ASD, which can be mediated by still poorly explored epigenetic modifications. We searched for methylation changes on blood DNA of 53 male ASD patients and 757 healthy controls using a methylomic array (450K Illumina), correlated the variants with transcriptional alterations in blood RNAseq data, and performed a case-control association study of the relevant findings in a larger cohort (394 cases and 500 controls). We found 700 differentially methylated CpGs, most of them hypomethylated in the ASD group (83.9%), with cis-acting expression changes at 7.6% of locations. Relevant findings included: (1) hypomethylation caused by rare genetic variants (meSNVs) at six loci (ERMN, USP24, METTL21C, PDE10A, STX16 and DBT) significantly associated with ASD (q-value <0.05); and (2) clustered epimutations associated to transcriptional changes in single-ASD patients (n=4). All meSNVs and clustered epimutations were inherited from unaffected parents. Resequencing of the top candidate genes also revealed a significant load of deleterious mutations affecting ERMN in ASD compared with controls. Our data indicate that inherited methylation alterations detectable in blood DNA, due to either genetic or epigenetic defects, can affect gene expression and contribute to ASD susceptibility most likely in an additive manner, and implicate ERMN as a novel ASD gene.
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PMID:Genetic and epigenetic methylation defects and implication of the ERMN gene in autism spectrum disorders. 2740 87

Members of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family mediate membrane fusion processes associated with vesicular trafficking and autophagy. SNAREs mediate core membrane fusion processes essential for all cells, but some SNAREs serve cell/tissue type-specific exocytic/endocytic functions, and are therefore critical for various aspects of embryonic development. Mutations or variants of their encoding genes could give rise to developmental disorders, such as those affecting the nervous system and immune system in humans. Mutations to components in the canonical synaptic vesicle fusion SNARE complex (VAMP2, STX1A/B, and SNAP25) and a key regulator of SNARE complex formation MUNC18-1, produce variant phenotypes of autism, intellectual disability, movement disorders, and epilepsy. STX11 and MUNC18-2 mutations underlie 2 subtypes of familial hemophagocytic lymphohistiocytosis. STX3 mutations contribute to variant microvillus inclusion disease. Chromosomal microdeletions involving STX16 play a role in pseudohypoparathyroidism type IB associated with abnormal imprinting of the GNAS complex locus. In this short review, I discuss these and other SNARE gene mutations and variants that are known to be associated with a variety developmental disorders, with a focus on their underlying cellular and molecular pathological basis deciphered through disease modeling. Possible pathogenic potentials of other SNAREs whose variants could be disease predisposing are also speculated upon.
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PMID:SNAREs and developmental disorders. 3295 7