Your Family Physician

May 12, 2009 (Chicago, Illinois) – Evidence is accumulating rapidly that a particular region of the human genome is associated with the development of autism. This information could help enormously in the development of treatments for the condition.

In a study presented here at the 8th Annual International Meeting for Autism Research and published online April 28 in the Annals of Human Genetics, a team of researchers found a clustering of mutations associated with autism in a region known as 5p14.1.

Another study, by some of the same researchers, published online April 28 in Nature, also linked his region with autism spectrum disorders. Located very close to this region are 2 genes coding for proteins known as cadherins that are involved in adhesion of neurons; these, in turn, are implicated in autism pathogenesis.

This is the first time that a particular gene region has been implicated in autism. "Our identification and replication of common variation [in families affected by autism] on chromosome 5p14.1 is a promising development in the struggle to understand the genetics of autism," said Margaret Pericak-Vance, PhD, lead investigator of the study published in the Annals of Human Genetics and a coauthor on the Nature paper. "Further functional analyses are needed to figure out the potential molecular mechanisms," she told Medscape Psychiatry.

Geraldine Dawson, PhD, the chief scientific officer for Autism Speaks and a coauthor of the Nature paper, notes that the convergence of findings from these 2 large-scale studies increases the likelihood that the 5p14.1 locus is, indeed, implicated in autism.

"However, keep in mind that this is going to be 1 of many [gene regions] that contribute to autism," said Dr. Dawson. "But this is 1 that now has been replicated and again points to specific aspects of brain function that we know are affected in autism. Ultimately, the goal will be to understand how these genes affect the biochemistry of the brain, so we can develop medications that could potentially repair that aspect of brain function."

The study led by Dr. Pericak-Vance, from the University of Miami's Miller School of Medicine, in Florida, involved the genotyping of 438 white families affected by autism and a comparison with the mutation locations found in another 457 white families who are part of the Autism Genetics Resource Exchange database.

Sophisticated DNA analyses revealed a clustering of mutations associated with autism risk in the 5p14.1 region. None of the mutations occurs within a known gene or a genetic sequence known to regulate a gene.

However, the investigators determined that lying nearby are several regions of potential relevance to autism, including the gene sequences coding for cadherin-9 and cadherin-10, a group of proteins involved in cell-cell junctions in the nervous system.

In the study published in Nature, Drs. Dawson, Pericak-Vance, and 54 coinvestigators performed similar, genomewide studies on 780 families with affected children, 1204 individuals affected by autism, and 6491 healthy controls. They found a clustering of genetic variants in the 5p14.1 region.

The study was supported by the National Institutes of Health and the Hussman Foundation. Dr. Pericak-Vance has no conflicts of interest to disclose.

Source : http://www.medscape.com/viewarticle/702685?sssdmh=dm1.470812&src=nldne