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 is a highly heritable neurodevelopmental disorder whose underlying genetic causes have yet to be identified. To date, there have been eight genome screens for autism, two of which identified a putative susceptibility locus on chromosome 16p. In the present study, 10 positional candidate genes that map to 16p11-13 were examined for coding variants: A2BP1, ABAT, BFAR, CREBBP, EMP2, GRIN2A, MRTF-B, SSTR5, TBX6, and UBN1. Screening of all coding and regulatory regions by denaturing high-performance liquid chromatography identified seven nonsynonymous changes. Five of these mutations were found to cosegregate with autism, but the mutations are not predicted to have deleterious effects on protein structure and are unlikely to represent significant etiological variants. Selected variants from candidate genes were genotyped in the entire International Molecular Genetics Study of Autism Consortium collection of 239 multiplex families and were tested for association with autism by use of the pedigree disequilibrium test. Additionally, genotype frequencies were compared between 239 unrelated affected individuals and 192 controls. Patterns of linkage disequilibrium were investigated, and the transmission of haplotypes across candidate genes was tested for association. Evidence of single-marker association was found for variants in ABAT, CREBBP, and GRIN2A. Within these genes, 12 single-nucleotide polymorphisms (SNPs) were subsequently genotyped in 91 autism trios (one affected individual and two unaffected parents), and the association was replicated within GRIN2A (Fisher's exact test, P<.0001). Logistic regression analysis of SNP data across GRIN2A and ABAT showed a trend toward haplotypic differences between cases and controls.
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PMID:Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT. 1583 Mar 22

Through several large-scale screening studies for autism spectrum disorders (ASD), a common 593-kb interstitial deletion of 16p11.2 has been identified as one of the most common genomic disorders associated with ASD. In this study, a familial occurrence of the 16p11.2 deletion was identified in association with hemivertebrae. The proband was a 3-year-old boy who showed developmental delay, displayed hyperactive but not autistic behavior, and had hemivertebrae, rib anomalies, and inguinal hernia. Familial investigation revealed that his mother shared the same deletion. Under the hypothesis of the existence of an unmasked mutation in the deletion region, we analyzed the sequence of the T-box 6 gene (TBX6) included in the deletion region, but did not detect any mutation. This suggests that haploinsufficiency of TBX6 can lead to vertebral malformation in low penetrance.
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PMID:A familial 593-kb microdeletion of 16p11.2 associated with mental retardation and hemivertebrae. 1977 79

The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism spectrum disorders (ASD). This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion disorder and the factors that modify the clinical phenotypes are currently unknown. Multiplex families with deletion offer unique opportunities for exploring the degree of heterogeneity and implicating modifiers. Here we reported the clinical and genomic characteristics of three 16p11.2 deletion carriers in a Chinese family. The father carries a de novo 16p11.2 deletion, and it was transmitted to the proband and sib. The proband presented with ASD, intellectual disability, learning difficulty, congenital malformations such as atrial septal defect, scoliosis. His dysmorphic features included myopia and strabismus, flat and broad nasal bridge, etc. While the father shared same neurodevelopmental problems as the proband, the younger brother did not show many of the proband's phenotypes. The possible unmasked mutation of TBX6 and MVP gene in this deleted region and the differential distribution of other genomic CNVs were explored to explain the phenotypic heterogeneity in these carriers. This report demonstrated the different developmental trajectory and discordant phenotypes among family members with the same 16p11.2 deletion, thus further illustrated the phenotypic complexity and heterogeneity of the 16p11.2 deletion.
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PMID:Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family. 2130 51