Mutations in three new genes have been linked to autism, according to new studies including one with investigators at Mount Sinai School of Medicine. All three studies include lead investigators of the Autism Sequencing Consortium (ASC). The findings, in a trio of papers revealing new genetic targets in autism, are published in the April 4th online issue of the journal Nature. The studies provide new insights into important genetic changes and the many biological pathways that lead to autism spectrum disorders (ASD).

Gene mutations are glitches in DNA which can put you at risk for a particular disease. The genes with mutations identified in the studies -- CHD8, SNC2A, and KATNAL2 -- were discovered with a new state-of-the-art genomics technology known as exome sequencing, where all protein coding regions of the genome, called the exome, are analyzed. The researchers say that with further characterization of the genes and sequencing of genes in thousands of families, they will be able to develop novel therapeutics and preventive strategies for autism.

"We now have a good sense of the large number of genes involved in autism and have discovered about 10 percent of them," said Joseph Buxbaum, PhD, Director of the Seaver Autism Center and Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience at Mount Sinai School of Medicine. "We need to study many more parents and their affected children if we are to uncover the genes important in ASD. As these genes are further characterized, this will lead to earlier diagnosis and novel drug development. This work is crucial for advancing autism treatment."

In the study, ASC researchers hypothesized that de novo mutations account for a substantial fraction of the risk for autism. De novo gene mutations are mutations that show up in affected children for the first time and result from mutations in the production of sperm or egg.

Founded by Dr. Buxbaum, the Autism Sequencing Consortium is an international group of autism genetics researchers that is working to identify additional genetic causes of autism through large-scale next-generation sequencing. The institutions involved in this study sequenced data from more than 500 families (both parents and the affected child), examining the protein-enriched areas of the genome.

"When the same mutations are found in multiple affected children and none are found in children without autism, we believe that we have identified mutations that collectively affect a higher proportion of individuals with autism," said Dr. Buxbaum. "Our studies revealed that the proteins encoded by the mutated genes interact with each other far more than expected, demonstrating significantly greater connectivity than would be expected."

Two other papers from groups participating in the Autism Sequencing Consortium are also featured in the same issue of Nature. Led by Matthew State, PhD, Yale School of Medicine, the first identified several highly disruptive mutations in genes associated with ASD. The results show that multiple variants on one gene identify risk factors for ASD. The second study led by Evan Eichler, PhD at the University of Washington discovered that certain mutations associated with ASD are mainly of paternal origin. Their findings also support previous research showing an increased risk of developing ASD in children of older fathers.

For children with autism, being born several weeks early or several weeks late tends to increase the severity of their symptoms, according to new research out of Michigan State University.

Additionally, autistic children who were born either preterm (prior to 37 weeks) or post-term (after 42 weeks) are more likely to self-injure themselves compared with autistic children born on time, revealed the study by Tammy Movsas of MSU's Department of Epidemiology.

Movsas, a postdoctoral epidemiology fellow in MSU's College of Human Medicine, said the study reveals there are many different manifestations of autism spectrum disorder, a collection of developmental disorders including both autism and Asperger syndrome. It also shows the length of the mother's pregnancy is one factor affecting the severity of the disorder.

While previous research has linked premature birth to higher rates of autism, this is one of the first studies to look at the severity of the disease among autistic children who had been born early, on time and late.

"We think about autism being caused by a combination of genetic and environmental factors," she said. "With preterm and post-term babies, there is something underlying that is altering the genetic expression of autism.

"The outside environment in which a preterm baby continues to mature is very different than the environment that the baby would have experienced in utero. This change in environment may be part of the reason why there is a difference in autistic severity in this set of infants."The study also found that babies born outside of normal gestational age (40 weeks) -- specifically very preterm babies -- showed an increase in stereotypical autistic mannerisms.

"Normal gestation age of birth seems to mitigate the severity of autism spectrum disorder symptoms, and the types of autistic traits tend to be different depending on age at birth," she said.

Though autism is often not diagnosed until the age of three, some children begin to show signs of developmental delay before they turn a year old. While not all infants and toddlers with delays will develop autism spectrum disorders (ASD), experts point to early detection of these signs as key to capitalizing on early diagnosis and intervention, which is believed to improve developmental outcomes.

According to Dr. Rebecca Landa, director of the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore, Md., parents need to be empowered to identify the warning signs of ASD and other communication delays.

"We want to encourage parents to become good observers of their children's development so that they can see the earliest indicators of delays in a baby's communication, social and motor skills," says Dr. Landa, who also cautions that some children who develop ASD don't show signs until after the second birthday or regress after appearing to develop typically.

For the past decade, Dr. Landa has followed infant siblings of children with autism to identify red flags of the disorder in their earliest form. Her research has shown that diagnosis is possible in some children as young as 14 months and sparked the development of early intervention models that have been shown to improve outcomes for toddlers showing signs of ASD as young as one and two years old.

Dr. Landa recommends that as parents play with their infant (6 -- 12 months), they look for the following signs that have been linked to later diagnosis of ASD or other communication disorders:

1. Rarely smiles when approached by caregivers 2. Rarely tries to imitate sounds and movements others make, such as smiling and laughing, during simple social exchanges 3. Delayed or infrequent babbling 4. Does not respond to his or her name with increasing consistency from 6 -- 12 months 5. Does not gesture to communicate by 10 months 6. Poor eye contact 7. Seeks your attention infrequently 8. Repeatedly stiffens arms, hands, legs or displays unusual body movements such as rotating the hands on the wrists, uncommon postures or other repetitive behaviors 9. Does not reach up toward you when you reach to pick him or her up 10. Delays in motor development, including delayed rolling over, pushing up and crawling

"If parents suspect something is wrong with their child's development, or that their child is losing skills, they should talk to their pediatrician or another developmental expert," says Dr. Landa. "Don't adopt a 'wait and see' perspective. We want to identify delays early in development so that intervention can begin when children's brains are more malleable and still developing their circuitry."

Traveling with a child who is prone to "autism wandering" poses more than the usual challenges of taking a family vacation.

Leslie Welch, of Raleigh, N.C., and her family visited Disney World when her son Josh, who has autism, was 5. They managed the outing with the aid of a well-detailed, daily security routine.

"We used a backpack leash even though it was way too small for him," Welch recalled. "I took his picture on my phone every morning [so if he got lost] I could show people what he was wearing that day."

She dressed him "in really bright clothes so he would stand out in a crowd" and made laminated ID cards because he's nonverbal. "I punched them with a hole puncher and tied them to his shoelaces," she recalled.

"I call it an achievement vacation," she said.

Children with autism may lack certain visual skills needed to be independent in adulthood, new study findings suggest.

For example, they might find it harder than other adults to find shoes in the bedroom or apples in the supermarket, according to researchers at the University of Bristol in the United Kingdom.

The study authors asked 20 children with autism and 20 typical children to press buttons to find a hidden target among multiple illuminated locations in a room. One side of the room had more targets than the other side.

The children with autism took longer to recognize patterns in the test structure that would help them choose where to search for the targets. The findings suggest that the ability to search for objects in a large-scale environment is less efficient and less systematic in children with autism compared to typical children, the researchers pointed out in a university news release.

The study findings are published in the Dec. 20 issue of the journal Proceedings of the National Academy of Sciences.

"The ability to work effectively and systematically in these kind of tasks mirrors everyday behaviors that allow us to function as independent adults, and this research offers an exciting opportunity to explore underlying skills that could help people with autism achieve independence," study co-author Dr. Josie Briscoe said in the news release.

A new study suggests that the handwriting problems that affect children with autism are likely to continue into their teenage years. The research is published in the November 16, 2010, issue of Neurology®, the medical journal of the American Academy of Neurology.

The study included 24 girls and boys between the age of 12 and 16. Half of the group had autism spectrum disorder and all of the teenagers scored within the normal range of perceptual reasoning on an IQ test.

The teens were given the Minnesota Handwriting Assessment Test, which uses a scrambled sentence to eliminate any speed advantage for more fluent readers. The sentence used on the test was "the brown jumped lazy fox quick dogs over." Participants were asked to copy the words in the sentence, making the letters the same size and shape as the sample using their best handwriting.

The handwriting was scored based on five categories: legibility, form, alignment, size and spacing. The teenagers' motor skills, including balance and timed movements, were also examined and given a rating.

The research found that the teenagers with autism earned 167 points out of 204 total possible points on the handwriting assessment, compared to the 183 points scored by teens in the group without autism. These results showed statistical significance in the study. The teenagers with autism also had motor skill impairments.

Handwriting performance in adolescents with autism was predicted by perceptual reasoning scores, which reflect a person's ability to reason through problems with nonverbal material. "That reasoning skills can predict handwriting performance suggests a possible strategy by which adolescents with autism could learn and utilize compensatory strategies to overcome motor impairments," said study author Amy Bastian, PhD, of the Kennedy Krieger Institute and Johns Hopkins School of Medicine in Baltimore, MD.

"While teenagers with autism are more likely to have handwriting problems, there are several techniques available to improve handwriting quality, such as adjusting pencil grip, stabilizing the writing hand with the opposite hand or forming letters more slowly. These therapies could help teens with autism to progress academically and develop socially," said Bastian.