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Review
. 2014 Oct:46 Pt 2:161-74.
doi: 10.1016/j.neubiorev.2014.02.015. Epub 2014 Apr 4.

Intellectual disability and autism spectrum disorders: causal genes and molecular mechanisms

Anand K Srivastava  1 , Charles E Schwartz  2
Affiliations
Review

Intellectual disability and autism spectrum disorders: causal genes and molecular mechanisms

Anand K Srivastava et al. Neurosci Biobehav Rev. 2014 Oct.

Abstract

Intellectual disability (ID) and autism spectrum disorder (ASD) are the most common developmental disorders present in humans. Combined, they affect between 3 and 5% of the population. Additionally, they can be found together in the same individual thereby complicating treatment. The causative factors (genes, epigenetic and environmental) are quite varied and likely interact so as to further complicate the assessment of an individual patient. Nonetheless, much valuable information has been gained by identifying candidate genes for ID or ASD. Understanding the etiology of either ID or ASD is of utmost importance for families. It allows a determination of the risk of recurrence, the possibility of other comorbidity medical problems, the molecular and cellular nature of the pathobiology and hopefully potential therapeutic approaches.

Keywords: Autism spectrum disorders; Intellectual disability; Molecular pathways; Neurodevelopmental disorder; Synaptic plasticity.

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Figures

Figure 1
Figure 1
Etiological causes of intellectual disability. Percentages are based on the evaluation of 15,484 individuals seen by the Greenwood Genetic Center.
Figure 2
Figure 2
Schematic diagram illustrating the complexity of the synaptic compartments and the molecular architecture of excitatory and inhibitory synapses. This figure depicts a subset of pre- and post-synaptic proteins regulating neurite outgrowth, synapse formation/maturation, synapse elimination and maintenance of a functional balance between excitatory and inhibitory synapses. The gene products implicated in neurodevelopmental disorders such as ID and ASD are shown in red type. The selected molecules and pathways shown here discussed in the text and elsewhere (Delorme et al. 2013; Ebert and Greenberg, 2013; van Bokhoven 2011; Waites and Garner, 2011).
Figure 3
Figure 3
Molecular function classification of genes associated with XLID, ID/ASD, developmental delay (DD), or entire human genome. Genes were classified for molecular function with Gene Ontology using the PANTHER genes classification tool (http://www.pantherdb.org/) and analyzed by the PANTHER whole genome functional analysis. GO molecular function category (Accession) and percent of genes hit against total number of Function hits are displayed as a pie chart for (A) the 101 X-linked intellectual disability (XLID) genes (total hits, 224), (B) the 705 genes associated with developmental delay prepared by the Greenwood Genetic Center (total hits, 892), (C) the 546 ASD/ID genes listed by SFARI (https://sfari.org/) (total hits, 796), and (D) the 18,331 human genes (total hits, 20,233).
Figure 4
Figure 4
Biological process classification of XLID, ID/ASD, DD genes or entire human genome. Genes were classified for biological process with Gene Ontology using the PANTHER gene classification tool and analyzed by the PANTHER whole genome functional analysis. GO biological process category (Accession) and percent of gene hit against total # Process hits are displayed as a pie chart for (A) the 101 XLID genes (total hits, 227), (B) the 705 genes associated with developmental delay prepared by the Greenwood Genetic Center (total hits, 1,651), (C) the 546 ASD/ID genes listed by SFARI (total hits, 1,638), and (D) the 18,331 human genes (total hits, 37,064).
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