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The genetic link between autism and structural cerebellar malformations

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United States

Autism has been consistently associated with abnormalities in the cerebellum, a brain structure important for motor coordination and sensory integration. Specifically, the cerebellum in autism has a smaller posterior portion and fewer Purkinje cells, which control its output. These abnormalities arise from disruptions in development, and this project hypothesizes that genes regulating cerebellar development may also cause autism. Notably, "autistic-like features" are often described for patients with cerebellar malformations. Dr. Millen's lab has been systematically searching the human genome for cerebellar malformation genes. So far they have identified 21 locations, all of which have some association with autism. Thus, although not all autism-related genes are involved in cerebellar development, every cerebellar malformation gene may be related to autism. In this research project Dr. Millen's fellow will test whether genes known to cause human cerebellar malformations also cause autism. The study will determine whether patients recruited for cerebellar malformations caused by specific genetic mutations meet the diagnostic criteria for autism. Patients recruited for their autism diagnosis and subsequently also diagnosed with a small posterior cerebellum will be examined for genetic mutations, namely changes in gene copy number, at defined cerebellar malformation genes. Mice with mutations in these cerebellar malformation genes will also be analyzed for evidence of behavioral changes relevant to autism. What this means for people with autism: These experiments will determine whether genes that cause cerebellar malformations also cause primary autism. If so, these genetic mutations could be used as diagnostic markers for this form of autism, and could lead to therapies aimed at reversing these disruptions of cerebellar development.