PTEN: linking cancer and autism

Recently, the phosphatase and tension homolog (PTEN) gene has been linked to the developmental austism spectrum disorders (ASDs) including Cowden Syndrome (CS). Once only seen as a gene related to tumor development and progression, PTEN has been reported to have increased mutations in children with austim, mental retardation, and macrocephaly or enlarge head size.

Loss of the normal activity of the dual-specific phosphatase PTEN, which functions to negatively regulate the phosphoinositol-3-kinase (PI3K) pathway, frequently results in over-proliferation of cells and cancer progression. PTEN may also play a role in normal neurological development since it has been found to be important in neruonal survival outgrowth, learning, and memory (1). Subsequently, mutations or the partial or even total loss of the gene then results in abnormal neurological function. In particular, one de novo missense mutation (D326N) in exon 8 of the gene has been found to be fairly common (2). Published reports show that mutant mouse models for PTEN exhibit marcrocephaly, increased soma size, and axonal and dendritic hypertropy. Since, the discovery of mutations in children have prompted diagnosis of autism (1).

ASDs are typically developmental disorders with an onset in children by the age of 3. In most cases of autism, children will have decreased social interactions, impaired communication, and often times compulsive behavior and the need for repetition. Interestingly, another connection between cancer and autism since CS is characterized by the development of hamartomas and is associated with increased cancer risks.

Taken together, this data and other evidence show the potential of PTEN to be considered an etiological factor of autism.