Progress in understanding the basis of autism is relevant to PWS for a number of reasons, including the high incidence of autistic behaviors in those with PWS (see, for example: Descheemaeker MJ, et al Pervasive developmental disorders in Prader-Willi syndrome: the Leuven experience in 59 subjects and controls. Am J Med Genet 140A:1136-42, 2006) and the association between autism and duplication of PWS region on chromosome 15 (Battaglia A. The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. Brain Dev. 27::365, 2005) But, getting to the bottom of what causes autism has proven very difficult.
There has been concern in the public that autism is caused by childhood vaccines, but a number of very large scientific studies donâ€™t support this concern, as detailed in reviews of the data by the US Centers for Disease Control and the Institute of Medicine (link to MMR/autism theory ).
Other studies have focused on the genetic component of autism, however, how many genes might contribute, and how the environment might influence the development of autism remains quite murky. In fact, a recent review article in Nature Neuroscience argues that autism is not one disorder, and should not be referred to as such. (See Focus on Childhood Developmental Disorders: Time to give up on a single explanation for autism , Nature Neuroscience Focus â€“ online free until Dec 2006). Whether or not autism is truly one disorder, or several, understanding the basis of any form of autism should provide good clues as to what goes wrong in all cases.
In this regard, there is strong evidence that genetic make up is a significant factor in the development of autism. But, despite a large number of attempts, identifying a single gene that causes or strongly contributes to autism has proven elusive. Now, an article just out in the Proceedings of the National Academy of Sciences presents compelling evidence that a particular variant of the MET gene on chromosome 7 may be associated with a high risk of developing autism. (Campbell DB et al, A genetic variant that disrupts MET transcription is associated with autism. Proc Natl Acad Sci USA 103:16834, 2006). This variant is associated with lower levels of MET expression. Itâ€™s not clear yet exactly why low levels of MET expression may predispose to autism, but it is known that the MET gene is important in brain growth and maturation, immune function, and gastrointestinal repair, all areas that have been suggested to be altered in autism.
Those in the cancer research world are already quite familiar with the MET gene because abnormally high levels of MET is often found in several types of cancer, where it is thought to promote cancer progression. The development of drugs to disrupt MET action and slow tumor growth is an active area of investigation. Although autism and cancer are seemingly unrelated, the involvement of MET in both processes is not necessarily surprising - many genes that normally promote cell growth during development can cause problems (e.g, cancer) if abnormally expressed when and where they shouldnâ€™t be.
Back to the issue of autism â€“ it will be important that the findings of this study be confirmed in additional families, but the data look quite robust and suggest many new areas of investigation, including investigating the role of the immune system and better understanding brain development, as well as very exciting possibilities including the development of a mouse model of autism and the development of new drugs, or modification of existing drugs that influence MET function.