February has brought a slew of news on several autism spectrum disorders. As the estimate of its prevalence was adjusted upward yet again, and the search for the genetic roots of autism spectrum disorders turned into an international manhunt, two recent papers brought hopeful news for the sufferers of one type of autism spectrum disorder, the disease Rett syndrome.

Autism is common, and its diagnosis has increased 10-fold over the past decade - though the actual number of affected individuals hasn't. In early February, the Centers for Disease Control and Prevention announced survey data showing that an autism spectrum disorder now is diagnosed in one out of every 150 children in the United States, up from previous estimates of one in 166. In New Jersey, the state with the highest prevalence of the six that were surveyed, the rate of autism spectrum disorders was about 1 percent.

As the number of diagnosed individuals has increased, though, former certainties about what causes the disease have vanished.

Once thought to be a mental disorder caused by that old standby, bad mothering, it is now conceptualized as "a neurodevelopmental disorder characterized by impairments in reciprocal social interaction, communication deficits and repetitive and restricted patterns of behavior and interests," as the authors of a recent paper in Nature Genetics write in their introduction.

In the paper, which was published online Feb. 18, scientists from a consortium of more than 50 institutions in almost 20 countries reported on using microarray analysis of roughly 1,500 families to search for both gene sequence and copy number variations that affect an individual's risk of developing autism.

The researchers identified two genes that are likely to play a role in autism susceptibility: neurexin 1, part of a family of genes which help build synapses that use the neurotransmitter glutamate, and a gene on chromosome 11 that still needs to be precisely identified.

As the authors point out in their paper, "the genetic architecture of [autism spectrum disorders] is complex." To date, scientific studies offer no easy answers about what causes autism. It is "associated with a recognized cause in only about 10 percent of individuals."

There is an exception to every rule, though, and Rett syndrome is one autism spectrum disorder that has an identified genetic cause, mutations in the MECP2 gene.

On a cellular level, the biggest problem in Rett syndrome seems to be that the faulty MECP2 expression damages neurons, leading to severe physical symptoms. Many Rett syndrome sufferers are wheelchair-bound, and breathing problems and Parkinson's-like tremors also are common.

However, those neurons, while damaged, do not die. And this suggested to some intrepid researchers at Edinburgh University and the University of Glasgow that it might be possible to repair them. In the Feb. 8, 2007, issue of Sciencexpress, they reported that it is possible to restore the faulty neurons in Rett syndrome to near-full functionality, implying the disease might be amenable to treatment longer than previously thought.

The researchers created reversible knockout mice in which the MECP2 gene normally was inactivated, but could be restored. To test whether there was a critical time period in which MECP2 needed to be functional, they let animals develop for different periods of time without MECP2 and then restored the gene's functioning.

Their first experiments were definitely in the good news category. In the bad news category, out of 17 mice, half were cured by the reactivation of MECP2. The other half died due to MECP2 toxicity.

When the researchers changed their techniques to allow for a more gradual reactivation of MECP2, however, the mice showed a rather spectacular comeback.

While there are many critical periods in brain development after which damage is not reversible, turning on MECP2 could lead to functional recovery of damaged neurons even in mice "that would have normally had only a few days to live" without any intervention, senior author Adrian Bird said in an interview posted to the Rett Syndrome Research Foundation website.

The authors followed up their work with another paper, this one in the Feb. 20, 2007, issue of the Proceedings of the National Academy of Sciences, suggesting a possible molecular mechanism for Rett syndrome.

MECP2 is a methylation protein, and the authors found that mutations that can be behind both Rett syndrome and a form of mental retardation known as ATRX disrupt the interaction of MECP2 with another chromatin-binding protein, which goes by the name of ATRX.

In the Sciencexpress paper, the authors cautioned that their findings "do not suggest an immediate therapeutic approach" for treating Rett syndrome. However, the findings do "establish the principle of reversibility in a mouse model and therefore raise the possibility that neurological defects seen in this and related human disorders are not irrevocable."