Scientists advance understanding of the role of a key brain protein in autism

Results of a genetic linkage analysis of PRKCB1 with autism published

Scientists working at IntegraGen SA, the personalized medicines company, have shown that variations in the gene for protein kinase C beta 1 (PRKCB1), a protein with an important role in brain function, are strongly associated with autism. This exciting finding suggests some answers to a number of previous, but unexplained, observations about autism and provides the potential for a mechanistic explanation for some of the characteristics of the condition. The results of the study are published today in the journal Molecular Psychiatry.

The PRKCB1 gene is expressed in the granule cells within the cerebellum (a region of the brain) where the PRKCB1 protein plays a central role in the transmission of signals by the granule cells to the Purkinje cells. It has previously been reported that there is a decreased number of both granule and Purkinje cells in the brains of autistic individuals and the association of PRKCB1 with autism reported in this study indicates that the cerebellum may play a key role in many of the brain activities that are impaired in autism. Another intriguing observation is that studies using animal models have shown that PRKCB1 is involved in auditory reversal learning. Considered in light of IntegraGen’s results, this suggests that deficiency of the protein might lead to the impairment of this learning capacity, as is frequently seen in autism.

“This is the first time that the protein PRKCB1, and the brain functions it is involved with, have been associated with autism,” explained Dr Jorg Hager, Chief Scientist at IntegraGen. “For this reason, we think that this is a significant development in the field of autism research and we hope it will make an important contribution to understanding the causes of the condition.”

Autism is a complex genetic disorder and it is believed that the combined action of a number of genes may increase a person’s susceptibility to the condition. Genetic researchers at IntegraGen have been using the Company’s novel GenomeHIP™ method to identify genes associated with autism. The Company has so far identified 12 regions of the genome linked to autism and, within those, has been able to specifically identify the region coding for PRKCB1. Work is continuing to identify further genes associated with autism within those loci identified.

As has been shown with this study, IntegraGen’s work to identify the genes involved in autism will contribute towards understanding the mechanisms behind the disease. IntegraGen plans to use its knowledge of the genetic risk factors to develop a genetic risk assessment test for the condition, based on the PRKCB1 and additional genes which it hopes to launch in 2006. The Company envisages that this will be used to help confirm diagnosis and to help patients and families better understand the condition and its causes. They hope that it may also prove to be a useful tool in assessing the risk of the condition developing when a child is still too young to show clear symptoms, so that informed decisions can be made by clinicians as to the use of interventional therapies as early and as appropriately as possible, at a time when they are known to be most effective.