In Brief

Mutations in a gene vital to brain development may predict the onset of autism, say researchers funded by the National Institutes of Health's (NIH) Collaborative Programs of Excellence in Autism (CPEA).

Autism, a developmental disability largely shrouded in mystery since its identification in 1941, typically manifests itself in the first three years of life and affects one in 500 individuals. Its stigmatizing symptoms include mental retardation, the inability to communicate, social withdrawal and repetitive hand and body movements.

The study, led by senior investigator Patricia M. Rodier, PhD, Jennifer Ingram, PhD and Christopher Stodgell, PhD, of the University of Rochester School of Medicine and Dentistry, tested 57 autistic people for a mutated version of the gene HOXA1, which plays a key role in fetal brain development. They found that 22--or 40 percent--had one copy of the variant.

Autism lacks a singular cause, and thus its genesis has posed a medical challenge. Researchers surmise that several genes, as well as early fetal exposure to toxins, maybe be key factors. In fact, the connection between prenatal exposure to thalidomide and the birth of autistic children with misshapen ears and nerve abnormality in the head and face prompted the team to investigate HOXA1.

Previous studies indicate that such defects transpire 20 to 24 days after conception--during the stage in which brain regions controlling the eyes, face, tongue, jaw and throat develop. Because mice engineered to lack HOXA1 exhibited equivalent aberrations, the researchers tested autistic patients for mutations of the analogous human gene. Their discoveries may foster understanding of how the brain changes when HOXA1 mutates, clearing a first and important hurdle in the race to advance the treatment and prevention of autism.

Rodier reports that only one person had two copies of mutated HOXA1, suggesting that children just need to inherit one copy of the variant gene to develop autism and that those with two die very early, before the genes can be detected. Parents and other family members were also tested, revealing that individuals who inherit the aberrant gene from their mothers exhibit stronger symptoms of autism than those who acquire the gene paternally. This trend bolsters several other studies, says Rodier, indicating that maternal inheritance is a strong determinant for developing autism.

"These findings strongly suggest that a gene controlling early brain formation may underlie the development of autism in a large number of cases," according to Duane Alexander, MD, Director of the National Institute of Child Health and Human Development and Chair of the NIH autism coordination committee.

Researchers hope this understanding of autism's cognitive causes and effects will point to better treatment methods and comprehension of the challenges autistic individuals face.

The study was published in the December issue of Teratology.

--E. O'CONNOR