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Lessons learned from studying syndromic autism spectrum disorders

Abstract

Syndromic autism spectrum disorders represent a group of childhood neurological conditions, typically associated with chromosomal abnormalities or mutations in a single gene. The discovery of their genetic causes has increased our understanding of the molecular pathways critical for normal cognitive and social development. Human studies have revealed that the brain is particularly sensitive to changes in dosage of various proteins from transcriptional and translational regulators to synaptic proteins. Investigations of these disorders in animals have shed light on previously unknown pathogenic mechanisms leading to the identification of potential targets for therapeutic intervention. The demonstration of reversibility of several phenotypes in adult mice is encouraging, and brings hope that with novel therapies, skills and functionality might improve in affected children and young adults. As new research reveals points of convergence between syndromic and nonsyndromic autism spectrum disorders, we believe there will be opportunities for shared therapeutics for this class of conditions.

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Figure 1: Timeline of key discoveries in the history of ASD research, with a focus on genetic advances.
Figure 2: Animal and cellular models for ASDs.

Debbie Maizels/Nature Publishing Group; KTSDESIGN/ Alfred Pasieka/Science Photo Library; Roxana Wegner

Figure 3: Mutations in syndromic and nonsyndromic ASD.

Debbie Maizels/Nature Publishing Group

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Correspondence to Huda Y Zoghbi.

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Sztainberg, Y., Zoghbi, H. Lessons learned from studying syndromic autism spectrum disorders. Nat Neurosci 19, 1408–1417 (2016). https://doi.org/10.1038/nn.4420

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