Is Autism Genetic?

From: Dr. Chun Wong If you have read my previous blog posts, you will know that I do not believe that autism is caused by just one thing but that it is a multifactorial condition which can be caused by a number of factors -so, is genetics one of these factors?

Research Linking Genetic Defects and Autism

There is a significant amount of research out there that links autism spectrum disorders with genetic defects. Here’s what studies have found:

• The work of geneticist Thomas Bourgeron - Bourgeron, a French geneticist, published a study in 2003 that showed that families of several autistic children had mutations in the NLGN3 and NLGN4X genes which led to a complete loss of function in these genes, triggering autism in the children. These two genes are responsible for the manufacture of neuroligin proteins which are needed by the body for the structure of nerve cell contacts.
• Gottingen Study - A study in Gottingen, published in the scientific journal “Neuron” and in Science Daily in September 2006, like Bourgeron’s work, showed that neuroligin proteins are essential for transmitting signals between nerve cell functions and that the brains of genetically altered mice, which did not have neuroligins, did not function properly because the synapses (the contact points at which the nerve cells communicate) never matured. The researchers of this study concluded that autism patients suffer with similar malfunctions due to neuroligin mutations.
• The work of Mark J Daly - Research headed by geneticist Mark J Daly of Massachusetts General Hospital has found that the risk of autism is increased one-hundredfold by “deletions or duplications of a specific small segment of chromosome 16″. The research team found this genetic defect in autistic children but not their parents, which suggests that sometime after fertilization there was spontaneous mutation in the location 16p11.2, a location known as a “genetic hot spot” because it is so susceptible to mutations.
• A defect in the CNTNAP2 gene - Three different research groups all reported in January 2008 (in the American Journal of Human Genetics” that a defective CNTNAP2 gene (also known as contactin-associated protein-like 2) was linked to autism and that it increased the risk of autism by 20% in children who inherited the gene from their mothers, although a mutated gene could be inherited from the father too.
• The work of Eric Morrow and Christopher Walsh - Morrow and Walsh, who led a research team from Harvard University, found that a set of six genes that are linked to brain development in the first year of a baby’s life are abnormal in many children with autism. The researchers also made the breakthrough that these 6 genes were not always completely deleted in children with autism, but that in some cases mutations in the surrounding control regions of the children’s DNA were keeping the genes “switched off”. This was encouraging as it could mean that therapy or medication could be used to activate the genes and allow normal brain development.
• Mitochondrial Disease and Autism - Dr John Shoffner, president of Medical Neurogenetics and an associate professor of biology at Georgia University, completed a “retrospective analysis” of 37 autistic children and found that 65% of them had mitochondrial defects. In other large studies, Shoffner says that 20% of children with autism have been found to “have markers of mitochondrial disease in the blood”.
• Gene mutations in 27 different genetic regions linked to autism - Research by geneticists from The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine and other institutions, found that there are 27 different genetic regions in autistic children where there are missing or extra copies of DNA segments, but that these are not found in healthy children. It is thought that the combination of genetic deletions and duplications interferes with gene function, disrupting the production of the proteins needed for proper brain development.
• US National Institutes of Health Research - A report by BBC News stated that research funded by the US National Institutes of Health found that genetic factors play a strong role in autism and that autism cases could be cut  by 15% if one common genetic variant was corrected. The research found that genetic variants of two genes found on chromosome 5 were linked to autism spectrum disorders.

  Those are just a few of the studies linking autism to genetics and autism expert Professor Simon Baron-Cohen, from the University of Cambridge, says that autism has now been linked to 133 genes and that further research is needed to understand how these genes interact and also to see how they interact with the environment.  In the BBC News report cited above, the UK’s National Autistic Society said:

“There is evidence to suggest that genetic factors are responsible for some forms of autism. However, the difficulty of establishing gene involvement is compounded by the interaction of genes and by their interaction with environmental factors. Various studies over many years have sought to identify candidate genes but so far inconclusively.”

So, genes probably are a factor in some cases of autism but they we should not consider genes in isolation. It could be that genetic abnormalities are making some children susceptible to environmental triggers and that it is a combination of genes and environmental factors that are causing autism spectrum disorders. But what about the link between autism and autoimmune diseases? I will be examing that next week.

Further Reading

Gottingen Study - http://www.sciencedaily.com/releases/2006/09/060925143554.htm Mark J Daly - http://articles.latimes.com/2008/jan/12/science/sci-autism12 Morrow and Walsh - http://www.timesonline.co.uk/tol/news/uk/health/article4311466.ece Shoffner - http://www.bio-medicine.org/medicine-news-1/Muscle-Weakness-Found-in-Some-Autistic-Children-16649-1/ Gene Mutations in 27 Different Genetic Regions - http://www.sciencedaily.com/releases/2009/06/090625202008.htm BBC News Report - http://news.bbc.co.uk/2/hi/health/8020837.stm