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)

Several independent genome scans have revealed excess allele sharing in an overlapping 40 cM region of 7q21-34 in autism. DLX6 and Piccolo (PCLO) at 7q21-q22 are two positional and functional candidate genes in autism. We have investigated a single nucleotide polymorphism (SNP) in exon 4 of the PCLO gene and a SNP in intron 1 of the DLX6 gene for linkage and association in autistic disorder using both qualitative and quantitative analyses. One hundred ninety-six multiplex autistic disorder families were tested using transmission disequilibrium and two-point affected sib pair linkage analysis. We found no evidence of association or linkage with the two intragenic markers. In addition, there was also no linkage or association between language and stereotypic behavior quantitative traits in autism and the SNPs. In conclusion, our studies suggest that these two SNPs in DLX6 and PCLO genes are not in linkage disequilibrium with autism.
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PMID:No association between single nucleotide polymorphisms in DLX6 and Piccolo genes at 7q21-q22 and autism. 1270 45

Mutations in MECP2 and Mecp2 (encoding methyl-CpG binding protein 2 [MeCP2]) cause distinct neurological phenotypes in humans and mice, respectively, but the molecular pathology is unclear. Recent literature claimed that the developmental homeobox gene DLX5 is imprinted and that its imprinting status is modulated by MeCP2, leading to biallelic expression in Rett syndrome and twofold overexpression of Dlx5 and Dlx6 in Mecp2-null mice. The conclusion that DLX5 is a direct target of MeCP2 has implications for research on the molecular bases of Rett syndrome, autism, and genomic imprinting. Attempting to replicate the reported data, we evaluated allele-specific expression of DLX5 and DLX6 in mouse x human somatic cell hybrids, lymphoblastoid cell lines, and frontal cortex from controls and individuals with MECP2 mutations. We identified novel single-nucleotide polymorphisms in DLX5 and DLX6, enabling the first imprinting studies of DLX6. We found that DLX5 and DLX6 are biallelically expressed in somatic cell hybrids and in human cell lines and brain, with no differences between affected and control samples. We also determined expression levels of Dlx5 and Dlx6 in forebrain from seven male Mecp2-mutant mice and eight wild-type littermates by real-time quantitative reverse-transcriptase polymerase chain reaction assays. Expression of Dlx5 and Dlx6, as well as of the imprinted gene Peg3, in mouse forebrain was highly variable, with no consistent differences between Mecp2-null mutants and controls. We conclude that DLX5 and DLX6 are not imprinted in humans and are not likely to be direct targets of MeCP2 modulation. In contrast, the imprinting status of PEG3 and PEG10 is maintained in MeCP2-deficient tissues. Our results confirm that MeCP2 plays no role in the maintenance of genomic imprinting and add PEG3 and PEG10 to the list of studied imprinted genes.
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PMID:DLX5 and DLX6 expression is biallelic and not modulated by MeCP2 deficiency. 1770 95

Linkage analysis has reported the chromosomal region 7q21 to be related with autism. This region contains an imprinting region with MECP2-binding sites, and DLX5 is reported to be modulated by MECP2. DLX5 and adjacent DLX6 are homeobox genes working in neurogenesis. From these points, DLX5 and DLX6 are candidate genes for autism. Therefore, we analyzed the expression of DLX5 and DLX6, and also PEG10 as a control in the lymphoblasts of autistic spectrum disorder (ASD) patients by real-time PCR to identify potential abnormality of expression. And we also analyzed DLX5 and DLX6 on ASD patients for mutation by direct sequence. The expression level of DLX5 was not different between ASD and controls but was higher in four ASD patients compared to controls. Clinical features of these four patients were variable. DLX5 expression was biallelic in two ASD patients and two controls, indicating that DLX5 was not imprinted. There was no mutation in DLX5 in ASD. Although DLX5 was not likely to play major role in ASD, genes relating to DLX5 expression and downstream of DLX5 are considered to be candidate genes for some of the ASD patients. In DLX6, we detected a G656A base change (R219H) in two ASD patients who were male siblings. DLX6 may contribute to the pathogenesis of ASD.
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PMID:Expression analysis and mutation detection of DLX5 and DLX6 in autism. 1919 2