ACC: Callosal Agenesis as a Window into Common Neurodevelopment Disorders

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Investigator: Elliott H. Sherr, MD, PhD
Sponsor: NIH National Institute of Neurological Disorders and Stroke

Location(s): United States

Description

The corpus callosum - the largest fiber tract in the human brain - connects and integrates the right and left sides of the brain. Absence of this structure isassociated with intellectual disability, autism, epilepsy, cerebral palsy and schizophrenia, as wel as many rare syndromes. We will use cutting-edge genetics tools to discover new genes that are important for development of the brain and corpus callosum and use animal models to investigate the underlying mechanisms.

The corpus callosum - the largest fiber tract in the human brain - connects and integrates the two cerebral hemispheres. Agenesis of the corpus callosum (ACC) affects 1 in 3-5,000 individuals, and occurs in both rare syndromes and common neurodevelopmental disorders such as intellectual disability, autism, epilepsy, cerebral palsy and schizophrenia. Recent evidence shows that genetic variation plays a critical role in ACC and in associated neurodevelopmental disorders, and that these genetic causes overlap. Yet for most affected individuals the causes are not known. Here we propose to leverage the power of our large and well-defined cohort of ACC subjects coupled with insights gained from animal models and recent advances in genome technology to 
(1) discover novel genes that cause rare ACC syndromes, 
(2) discover novel genes that cause or contribute to isolated and neurodevelopmental disorder-associated ACC, and 
(3) utilize mouse models to conduct functional confirmation of candidate genes.