Family‐based association study between autism and glutamate receptor 6 gene in Chinese Han trios

Mei, Shuang; Liu, Jing; Jia, Mei; Jian, Yang; Wu, Su; Gong, Xiao Hong; Ling, Yan; Ruan, Yan; Yang, Xuyan; Zhang, Dai

doi:10.1002/ajmg.b.30025

Cited by 91 publications

(55 citation statements)

References 14 publications

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“…15 Moreover, glutamatergic neurons originate in brain regions implicated in autism, and glutamate antagonists can cause symptoms similar to those of autism. 45 Four studies have specifically looked for association between GRIK2 and autism, with three finding positive evidence 17,18,46 and one study failing to do so. 47 In their recent genome-wide association paper, Wang et al 11 report top associations (Po0.01) for 26 candidate genes.…”

Section: Discussionmentioning

confidence: 99%

Linkage and candidate gene studies of autism spectrum disorders in European populations

et al. 2010

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the EU Autism MOLGEN Consortium 8Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate previously reported associations. In this paper, we investigate previously implicated genomic regions for a role in ASD susceptibility, using four cohorts of European ancestry. Initially, a 384 SNP Illumina GoldenGate array was used to examine linkage at six previously implicated loci. We identify linkage approaching genome-wide suggestive levels on chromosome 2 (rs2885116, MLOD¼1.89). Association analysis showed significant associations in MKL2 with ASD (rs756472, P¼4.31Â10 À5 ) and between SND1 and strict autism (rs1881084, P¼7.76Â10 À5 ) in the Finnish and Northern Dutch populations, respectively. Subsequently, we used a second 384 SNP Illumina GoldenGate array to examine the association in seven candidate genes, and evidence for association was found in RELN (rs362780, P¼0.00165). Further increasing the sample size strengthened the association with RELN (rs362780, P¼0.001) and produced a second significant result in GRIK2 (rs2518261, P¼0.008). Our results strengthen the case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility, as well as identifying two new potential candidate genes, MKL2 and SND1.

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Section: Discussionmentioning

confidence: 99%

Linkage and candidate gene studies of autism spectrum disorders in European populations

et al. 2010

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“…Association and linkage studies suggested its involvement in autism. 20,21 Glutamate receptors mediate the majority of excitatory neurotransmission in the brain. 22 Haploinsufficiency of this gene might cause mental retardation.…”

Section: Discussionmentioning

confidence: 99%

Detailed phenotype–genotype study in five patients with chromosome 6q16 deletion: narrowing the critical region for Prader–Willi-like phenotype

et al. 2008

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Most patients with an interstitial deletion of 6q16 have Prader-Willi-like phenotype, featuring obesity, hypotonia, short hands and feet, and developmental delay. In all reported studies, the chromosome rearrangement was detected by karyotype analysis, which provides an overview of the entire genome but has limited resolution. Here we describe a detailed clinical presentation of five patients, two of whom were previously reported, with overlapping interstitial 6q16 deletions and Prader-Willi-like phenotype. Our patients share the following main features with previously reported cases: global developmental delay, hypotonia, obesity, hyperphagia, and eye/vision anomalies. All rearrangement breakpoints have been accurately defined through array-CGH at about 100 Kb resolution. We were able to narrow the shortest region of deletion overlap for the presumed gene(s) involved in the Prader -Willi-like syndrome to 4.1 Mb located at 6q16.1q16.2. Our results support the evidence that haploinsufficiency of the SIM1 gene is responsible for obesity in these patients. A possible involvement of the GRIK2 gene in autistic-like behaviour, of POPDC3 in heart development, and of MCHR2 in the control of feeding behaviour and energy metabolism is also hypothesized.

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“…Two studies have found evidence for association of different SNPs in the Glutamate receptor 6 (GluR6) 162,163 Only one of these SNPs might have possible functional implications, and most were located in introns. However, given the importance of glutamate in brain development, learning and memory, 164 the positive linkage findings on 6q21 in two studies (Table 1) as well as post-mortem evidence of brain abnormalities of the glutamate neurotransmitter system in autism, 165 this candidate gene seems to be of relevance in the pathogenesis of AD.…”

Section: Chromosomementioning

confidence: 99%

The genetics of autistic disorders and its clinical relevance: a review of the literature

2006

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Twin and family studies in autistic disorders (AD) have elucidated a high heritability of the narrow and broad phenotype of AD. In this review on the genetics of AD, we will initially delineate the phenotype of AD and discuss aspects of differential diagnosis, which are particularly relevant with regard to the genetics of autism. Cytogenetic and molecular genetic studies will be presented in detail, and the possibly involved aetiopathological pathways will be described. Implications of the different genetic findings for genetic counselling will be mentioned.

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Family‐based association study between autism and glutamate receptor 6 gene in Chinese Han trios

Cited by 91 publications

References 14 publications

Linkage and candidate gene studies of autism spectrum disorders in European populations

Linkage and candidate gene studies of autism spectrum disorders in European populations

Detailed phenotype–genotype study in five patients with chromosome 6q16 deletion: narrowing the critical region for Prader–Willi-like phenotype

The genetics of autistic disorders and its clinical relevance: a review of the literature

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