Examination of NRCAM, LRRN3, KIAA0716, and LAMB1as autism candidate genes

Hutcheson, Holli; Olson, Lana M.; Bradford, Yuki; Folstein, Susan E.; Santangelo, Susan L.; Sutcliffe, James S.; Haines, Jonathan L.

doi:10.1186/1471-2350-5-12

Cited by 56 publications

(48 citation statements)

References 33 publications

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“…Molecular Psychiatry study 185 similarly assessed several SNPs in the LAMB1 gene, and found association with the disorder for a haplotype consisting of two SNPs in intron 25. No exonic SNPs were associated with AD in this study.…”

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confidence: 99%

“…The positive finding in the ASP, however, was again not replicated in the singleton IMGSAC sample, 184 and no association was found for variants in the NRCAM gene in the second study. 185 Taken together, LAMB1 remains an interesting candidate gene for AD, as LAMB1 encodes for the b1 chain of laminin, which is an important glycoprotein promoting neuronal migration and neurite outgrowth in the developing nervous system. 186,187 Variants in the protein-tyrosine phosphatase, receptor-type, zeta-1 (PTPRZ1) gene, which is highly expressed in the brain during embryogenesis, 188 have been assessed by two studies.…”

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confidence: 99%

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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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confidence: 99%

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confidence: 99%

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

2006

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“…Based on elaborate research regarding possible imprinted genes, fragile sites and duplications, candidate genes for several developmental disorders have been suggested, including candidate genes for autism. 71 Interestingly, for this chromosome there is a considerable overlap of the cytogenetic regions of interest and the results from linkage 25,72 and association studies [38][39][40]42,73,74 (see Figure 1, Tables 1 and 2). Of special interest are the regions 7q21-q22 and 7q31-q32.…”

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confidence: 99%

Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism

et al. 2005

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The identification of the candidate genes for autism through linkage and association studies has proven to be a difficult enterprise. An alternative approach is the analysis of cytogenetic abnormalities associated with autism. We present a review of all studies to date that relate patients with cytogenetic abnormalities to the autism phenotype. A literature survey of the Medline and Pubmed databases was performed, using multiple keyword searches. Additional searches through cited references and abstracts from the major genetic conferences from 2000 onwards completed the search. The quality of the phenotype (i.e. of the autism spectrum diagnosis) was rated for each included case. Available specific probe and marker information was used to define optimally the boundaries of the cytogenetic abnormalities. In case of recurrent deletions or duplications on chromosome 15 and 22, the positions of the low copy repeats that are thought to mediate these rearrangements were used to define the most likely boundaries of the implicated 'Cytogenetic Regions Of Interest' (CROIs). If no molecular data were available, the sequence position of the relevant chromosome bands was used to obtain the approximate molecular boundaries of the CROI. The findings of the current review indicate: (1) several regions of overlap between CROIs and known loci of significant linkage and/or association findings, and (2) additional regions of overlap among multiple CROIs at the same locus. Whereas the first finding confirms previous linkage/association findings, the latter may represent novel, not previously identified regions containing genes that contribute to autism. This analysis not only has confirmed the presence of several known autism risk regions but has also revealed additional previously unidentified loci, including 2q37, 5p15,

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“…Genomewide linkage scans, an unbiased approach to localize genetic factors, have identified several chromosomal regions as promising locations for autism vulnerability genes, including peaks on chromosomes 2q, 7q, 15q, and 17q (5)(6)(7)(8). This genetic approach to identify susceptibility genes is very powerful, but the heterogeneity present within autism families has led thus far to mixed success in identifying candidate genes (9,10).…”

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A genetic variant that disrupts MET transcription is associated with autism

Campbell¹,

Sutcliffe

Ebert³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

387

352

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There is strong evidence for a genetic predisposition to autism and an intense interest in discovering heritable risk factors that disrupt gene function. Based on neurobiological findings and location within a chromosome 7q31 autism candidate gene region, we analyzed the gene encoding the pleiotropic MET receptor tyrosine kinase in a family based study of autism including 1,231 cases. MET signaling participates in neocortical and cerebellar growth and maturation, immune function, and gastrointestinal repair, consistent with reported medical complications in some children with autism. Here, we show genetic association (P ‫؍‬ 0.0005) of a common C allele in the promoter region of the MET gene in 204 autism families. The allelic association at this MET variant was confirmed in a replication sample of 539 autism families (P ‫؍‬ 0.001) and in the combined sample (P ‫؍‬ 0.000005). Multiplex families, in which more than one child has autism, exhibited the strongest allelic association (P ‫؍‬ 0.000007). In case-control analyses, the autism diagnosis relative risk was 2.27 (95% confidence interval: 1.41-3.65; P ‫؍‬ 0.0006) for the CC genotype and 1.67 (95% confidence interval: 1.11-2.49; P ‫؍‬ 0.012) for the CG genotype compared with the GG genotype. Functional assays showed that the C allele results in a 2-fold decrease in MET promoter activity and altered binding of specific transcription factor complexes. These data implicate reduced MET gene expression in autism susceptibility, providing evidence of a previously undescribed pathophysiological basis for this behaviorally and medically complex disorder.autism spectrum disorder ͉ association ͉ candidate gene ͉ hepatocyte growth factor ͉ hepatocyte growth factor receptor

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Examination of NRCAM, LRRN3, KIAA0716, and LAMB1as autism candidate genes

Cited by 56 publications

References 33 publications

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

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

Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism

A genetic variant that disrupts MET transcription is associated with autism

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