Wednesday, 22 August 2012

Gene Mutations Linked to Autism


Nina Sclavos

Gene mutations are abnormalities in DNA which can occur in two ways; they can be inherited from a parent or acquired during a person’s lifetime.  In some cases where mutations cause a protein to malfunction or to be deleted entirely, normal development can be disrupted or a medical condition can be precipitated.  A condition caused by gene mutation is referred to as a genetic disorder (USNLM, 2012).   In order for successful detection, prevention and treatment of such disorders, a good understanding of the genes and disrupted molecular pathways of the disease needs to be gained.  This is the case with autism spectrum disorders (ASDs). ASDs include Autism, Asperger’s Syndrome and Pervasive Development Disorder.  Currently in Australia, 1 in 160 children between the ages of 6 – 12 are diagnosed with an ASD, with the prevalence of such disorders doubling every 5 years (Williams & Wray, 2009).  Although the cause of ASDs has not been discovered, research has indicated significant genetic links.  In fact, in recent years there have been many studies which have found that mutations in several genes are associated with the disorder.  Three papers published in the journal Nature in April this year have added to such evidence.

The studies included lead investigators of the Autism Sequencing Consortium who reported the largest exome sequencing efforts to date.  Exome sequencing is a relatively new technology which analyses all protein-enriched regions of the genome.  For at least 70% of cases of ASD, the underlying genetic cause is unknown (O’Roak et al., 2012).  The study formed the hypothesis that de novo mutations account for a substantial fraction of the risk for developing ASD in ‘sporadic’ families with no previous history of ASD.  De novo mutations occur only in an egg or sperm cell or just following fertilisation.  The sequencing data of over 500 families were used in the investigation, with particular attention paid to the exomes. By sequencing all coding regions for parent-child trios, combined with sequencing the exomes of 50 unaffected siblings, a snapshot of autism-characterised genes was created (Saunders et al., 2012).  Specifically, the study provided strong evidence that the presence of the three gene mutations in particular, increased the risk of ASDs (Neale et al 2012).  These genes were identified as: CHD8, SNC2A and KATNAL2 (Saunders et al., 2012, O’Roak et al., 2012 & Neale et al., 2012).   The studies also found that de novo mutations are ‘overwhelmingly paternal in origin and positively correlated with paternal age’ reporting a ‘modest increased risk’ for children of older fathers to develop ASD as the results indicated an increased mutation rate (Neale et al., 2012).  Interestingly, the study discovered that trio-based exome sequencing might be an effective approach for identifying new autism genes moving forward (O’Roak et al., 2012). 

Advancements such as these are crucial as they provide further insight into the genetic changes and many biological pathways that lead to ASD.  However, a comprehensive understanding of this complex genetic condition is not yet achievable with only an estimated 10 per cent of genes involving autism presently having been discovered (Baxbaum, 2012).  This is why the sequencing of genes in as many ASD affected families as possible is important in order to further identify potential genes, develop therapeutic treatments and form preventative strategies for the numerous sufferers of this complex developmental disorder.   


Buxbaum, J. (2012) Mutations in Three Genes Linked to Autism Spectrum Disorders. Retrieved via internet explorer on 8/8/12 via

Neale et al. (2012, April 4) Patterns and rates of exonic de novo mutations in autism spectrum disorders. Published in Nature. Vol 484, pp 242-245.  

O’Roak et al. (2012) Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Published in Nature. Volume 484, pp 246-250.

Sanders et al. (2012) De novo mutations revealed by whole-exome sequencing are strongly associated with autism.  Published in Nature, Vol 484, pp 237-241. 

State, M., Eichler, E. & Daly, M. et al. (2012) Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Published in Nature Genetics. Volume 4: 585-589. 

U.S. National Library of Medicine (USNLM) Genetics Home Reference.  Retrieved via Internet Explorer on 10/8/12 via

Williams, K. &  Wray, J. (2009) The Prevelence of Autism in Australia. Australian Advisary Board on Autism Spectrum Disorders. Sydney. 

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