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Autism and the 22q11.2 Microdeletion Syndrome

Systems Analysis of the 22q11.2 Microdeletion Syndrome Converges on a Mitochondrial Interactome Necessary for Synapse Function and Behavior

This study focused on the 22q11.2 deletion syndrome (DiGeorge syndrome), which increases an individual's risk for the development of autism by 15-50%. Drosophila (Fruit flies) were used to study the function of these proteins in neurons. Individuals with the 22q11.2 microdeletion gene are also at the highest risk of schizophrenia. Researchers at the Emory University Department of Medicine focused on mitochondrial genes that are associated with this deletion, SLC25A1 and SLC25A4. These are both transporters that are important for the function of the electron transport chain which is where we get our energy for aerobic respiration. The connection between this and autism are not yet clear.

To understand the mechanisms that generate the pathology displayed by the 22q11.2 microdeletion, a model organism is required (as primitive exploratory research in humans is frowned upon). This study aims to unbiasedly determine if the 22q11.2 microdeletion can be modeled by Df(16)A+/- mice, who present an analogous pathology. By comparing human fibroblasts and Df(16)A+/- brain cells, the researchers identified protein "malfunctions" in SLC25A1-SLC25A4 mitochondrial interactome. Here, this research paper solidifies and expands other studies which have strongly tied mitochondrial transporter deficiencies to neurodegenerative effects. This gives us a promising outlook in the genetic basis on autism and related disorders.

The authors highlight the strong proteomic agreement between the mouse model and the human fibroblasts as a key contributor to the success of their projects. However, the use of human fibroblasts limits the discovery of proteomic changes to those that are systemic (affecting all cells) as opposed to the specific implications of the microdeletion in neuron cells. Additionally, further confirmation will be required to solidify the cause-and-effect relationship of SLC25A1-SLCA4 transporters and neuron-specific pathology.

How this applies to autism

Elucidating molecular mechanisms that are affected by the 22q11.2 microdeletion will enable us to learn more about the nuances of the neurodevelopmental disorders that are correlated with the deletion. Early detection and inheritance studies will benefit greatly. Discovering more about these disorders and their associated mechanisms will aid in the development of novel therapeutics for these neurodevelopmental disorders!

Acknowledgements: Thank you to Dr. Cortine Hartwig of the Emory University School of Medicine for sending us her research and taking the time to explain it to us.

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