Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting

@article{Betancur2011EtiologicalHI,
  title={Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting},
  author={Catalina Betancur},
  journal={Brain Research},
  year={2011},
  volume={1380},
  pages={42-77}
}
  • C. Betancur
  • Published 22 March 2011
  • Psychology, Medicine
  • Brain Research
There is increasing evidence that autism spectrum disorders (ASDs) can arise from rare highly penetrant mutations and genomic imbalances. The rare nature of these variants, and the often differing orbits of clinical and research geneticists, can make it difficult to fully appreciate the extent to which we have made progress in understanding the genetic etiology of autism. In fact, there is a persistent view in the autism research community that there are only a modest number of autism loci… 
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References

SHOWING 1-10 OF 591 REFERENCES
Phenomic determinants of genomic variation in autism spectrum disorders
TLDR
The findings indicate increased prevalence of pCNVs in subjects with microcephaly and the relationship between parental ages at delivery and CNV load and pathogenicity was also explored.
Functional impact of global rare copy number variation in autism spectrum disorders
TLDR
The genome-wide characteristics of rare (<1% frequency) copy number variation in ASD are analysed using dense genotyping arrays to reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia.
TLDR
These data demonstrate that deletion 17q12 is a recurrent, pathogenic CNV that confers a very high risk for ASD and schizophrenia and show that one or more of the 15 genes in the deleted interval is dosage sensitive and essential for normal brain development and function.
Evaluation of autism traits in Angelman syndrome: a resource to unfold autism genes
TLDR
E evaluation of the behaviour domain suggested that repetitive sensory and motor behaviours correlate with a low developmental profile rather than being specific to autism, and classification of co-morbid AD/ASD vs the classification of less affected bASD.
Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation.
TLDR
Most of these CNVs (which contain genes involved in neurotransmission or in synapse formation and maintenance) are present in the 3 pathologic conditions (sch schizophrenia, autism, and mental retardation), supporting the existence of shared biologic pathways in these neurodevelopmental disorders.
Disruption at the PTCHD1 Locus on Xp22.11 in Autism Spectrum Disorder and Intellectual Disability
TLDR
Genetic analysis in thousands of patients and control subjects suggests that the PTCHD1 gene may be part of the Hedgehog signaling pathway, which is important in embryonic development, and suggests that this locus is involved in ~1% of individuals with ASD and intellectual disability.
Genome-Wide Analyses of Exonic Copy Number Variants in a Family-Based Study Point to Novel Autism Susceptibility Genes
TLDR
To pinpoint genes likely to contribute to ASD etiology, high density genotyping was performed in 912 multiplex families from the Autism Genetics Resource Exchange collection and contrasted results to those obtained for 1,488 healthy controls.
Features of Autism in Rett Syndrome and Severe Mental Retardation
TLDR
Controlling for developmental level and motor ability, girls with RS scored more highly than those with SMR on the Sensory and Relating subscales, and there were no group differences on the Body and Object use, Language and Social and Self-help subscales.
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
TLDR
Several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls, and duplications 55 kilobases upstream of complementary DNA AK123120 indicate that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.
X chromosome and infantile autism
TLDR
Results from the first association study described using markers of X chromosome in infantile autism encourage research on this chromosome, which could be considered as a significant genetic component of the multifactorial etiology of autism.
...
1
2
3
4
5
...