Autism is a developmental disorder that impairs social behavior and communication in children before the age of 3. While the current estimate of a sibling recurrence risk is at 15%, the population of children with an autism spectrum disorder is about 1 per 150. How has autism become so common within these young children? Geneticists have found a couple of important genes called NHE9 and DIA1 as possible disruptions to cause the disorder.
A study done by Morrow et. al, investigated the coding regions of NHE9, a nearby gene encoding a membrane protein that exchanges intracellular H-ions for sodium. It was sequenced to find a loss of function mutation in a nonconsanguineous family. They also found a gene called DIA1 (deleted in autism1), an uncharacterized protein, to be completely removed from chromosome 3q.
Morrow et. al, used DNA microarrays to study various consanguineous families from the Middle East and were able to identify common inherited regions of affected individuals with homozygous segments. These individuals were completely deficient for the genes in the deleted intervals and these regions were predicted to cause the autism spectrum disorder in the family.
These scientists also found similar loss of function mutations causing an epileptic phenotype in mice. These mutations also caused a phenotype with autistic symptoms and epilepsy in the related NHE6 gene. Mice can be tested for autism by monitoring the reduction of social response to other individuals. They can also be startled by an auditory signal in order to measure its response, frozen time, and its force applied to the floor. Combining these findings support dysregulation of NHE9 as a contributing or casual factor in a family with affected individuals.
Overall, this study points out some important clues towards autism susceptibility. Since autism is a neurodevelopmental disorder, the genes mentioned above have expression changes due to stimulation of neuronal activity. As the brain develops after birth, synapses mature as a function of experience-dependent neuronal activity and of the gene-expression that follows. Scientists have been able to establish dysregulation of synaptic development as an idea for autism research. Although more studies are necessary to confirm this idea, the possibility that dysregulation of these genes results in synaptic development disruption is a fascinating hypothesis.
Sutcliffe, James S. Insights into the Pathogenesis of Autism. Science 11 July 2008: 208- 209. [DOI:10.1126/science.1160555]
Anders J, Baxter B, Pi C, Dunn C, Fahimi F, Yamdagni N. Novel Measures of Mouse Social Behavior. December 2004. http://homepages.cae.wisc.edu/~bme402/mouse_stress/reports/Final_Paper.pdf
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