Certain gene mutations can compromise normal protein functioning, leading to heritable diseases. Although researchers have identified a few genes that are disrupted in some people with autism, for the most part, autism spectrum disorders remain genetically undefined. Mutations in the AUTS2 gene, which most likely result in truncated versions of the AUTS2 protein, have been found in several people who exhibit autism symptoms.

The most common genetic cause of autism is the deletion or duplication of a small region of human chromosome 16. Although these genetic changes account for only about 1 percent of all cases of autism, they predictably result in autism symptoms.

A major obstacle impeding the development of effective treatments for autism is the complexity of factors, such as genetic mutations, epigenetics and environmental influences that contribute to the disorder. However, research over the past few years suggests that ‘hot spots’ of cellular dysfunction are shared across autism spectrum disorders of different etiologies.

Despite tremendous efforts to genetically and phenotypically characterize individuals with autism, we are still at the earliest stages of understanding how autism occurs. The vast majority of individuals with autism have mutations in one copy of each of multiple genes (heterozygous mutations), and these mutations interact with each other in ways that we do not yet understand.

Perturbed neuronal arborization, or branching, and defects in long-range connectivity are likely to be shared mechanisms in many forms of severe autism. Neurotrophic factors (proteins that play a role in the growth and maintenance of neurons) and their cognate receptors, such as brain-derived neurotrophic factor (BDNF) and TrkB, respectively, govern the development of neuronal circuitry, in part, through signaling at the level of intracellular organelles known as endosomes. The protein NHE6 localizes within the cell membranes that form endosomes. Moreover, through its role in mediating the transport of protons (H+) out of endosomes in exchange for the import of sodium (Na+) ions, it contributes to modulating endosome acidity.

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by impairments in social interaction and communication, and restricted, stereotyped behaviors that manifest in early childhood. Research findings have identified widespread changes in the immune system in children with autism.

The chemical messenger serotonin has long been associated with autism. Serotonin is made in the blood and in the brain. In the brain, it is made by a specialized group of neurons in the brainstem and functions as a neurotransmitter, influencing the activity of neurons in virtually all regions. How abnormal serotonin function contributes to some of the key behaviors that define autism is not clear, but serotonin has been shown to affect the development and function of synapses, the junctions between brain cells. This is consistent with the idea that autism might be a disorder of the synapse.

Autism spectrum disorder is widely regarded as one of the most severe childhood psychiatric conditions. The root causes of this disorder have generally been viewed as either genetic or environmental. The interaction between genetic and environmental factors has not been investigated widely, however, despite the fact that synergistic effects have been found for other neurodevelopmental disorders such as depression.

The deletion of 27 genes in the 16p11.2 chromosomal region is associated with autism spectrum disorders, intellectual disability and obesity. To study the underlying cellular, molecular and anatomical basis of autism, Ricardo Dolmetsch and his colleagues at Stanford University in California have generated a mouse that lacks the same 27 genes on a corresponding chromosome in the mouse genome. Their goal, in collaboration with Jacqueline Crawley’s lab, is to characterize the neuroanatomical, neurophysiological and behavioral features of these mice.