From The Quarterly, Fall 2010

New findings by a NARSAD Independent Investigator and his colleagues provide important new clues that may help account for one of the great mysteries in neuroscience: why autism spectrum disorders (ASDs) occur much more frequently in boys than girls.

NARSAD Independent Investigator John B. Vincent, Ph.D., and colleagues at the University of Toronto’s Centre for Addiction and Mental Health have identified a series of gene copy-number variations, or CNVs, that interrupt the function of a single g ene — PTCHD1 — among members of some families affected by ASDs, as well as intellectual disabilities, or IDs. CNVs are structural mutations of the genome. We all have some CNVs, and in most cases they are innocuous. Certain ones fall in regions of the genome containing a gene vital for basic functions.

Thanks to the work of Dr. Vincent’s group, we now know one such area is a tiny segment of the socalled “X” chromosome occupied by the PTC HD1 gene. In a study sample that included more than 2,000 people diagnosed with an ASD or ID, and 10,000 healthy people, the team discovered CNVs correlating with PTCHD1 in about 1 percent of those diagnosed and in none of the healthy controls.

This indicates two things. First, def ects impairing the PTCHD1 gene are strongly associated with ASDs, albeit in a subset (1 percent) of patients. (Other cases are likely caused by other CNVs, or by other factors.) Second, the fact that PTCHD1 is on the X chromosome helps to explain the gender bias in autism, in at least 1 percent of cases. How? All males have only one X chromosome in every cell, inherited from their mother; it is paired with a “Y” chromosome, inherited f rom their father.

All females, who lack the “Y” altogether, have two copies of the X chromosome. If a CNV disrupting the PTCHD1 gene can cause ASDs, as the team suspects, then boys who have the mutation are at high risk to have the illness since they only have one copy of the gene. Girls, on the other hand, have two copies — one on each of their two X chromosomes; so there is one to fall back on if th ere is a CNV or other disabling mutation on one of them. Girls with one bad copy would, however, remain carriers of ASDs.

Dr. Vincent hopes that earlier detection of ASDs and IDs will be possible as a result of the new findings. He also hopes that with further investigation into PTCHD1, more effective interventions and therapies will be developed to treat ASDs and IDs.