Mutations in the exocyst component EXOC2 cause severe defects in human brain development.

Area of Science:

• Cell Biology
• Neuroscience
• Genetics

Background:

• The exocyst complex is crucial for vesicle transport and membrane fusion at the plasma membrane.
• Exocyst subunits are essential for normal neuronal development and function.

Purpose of the Study:

• To investigate the role of the exocyst subunit EXOC2 (Sec5) in human neurological disorders.
• To identify pathogenic variants in EXOC2 and elucidate their functional consequences.

Main Methods:

• Genetic analysis of affected individuals and families.
• Assessment of exocytosis and vesicle fusion in patient-derived cells.
• Evaluation of Arl13b localization to primary cilia.

Main Results:

• Identified pathogenic variants in EXOC2 associated with severe developmental delay, dysmorphism, brain abnormalities, epilepsy, and motor deficits.
• Demonstrated that EXOC2 variants lead to reduced exocytosis and vesicle fusion.
• Observed defective Arl13b localization to primary cilia in cells with EXOC2 mutations.

Conclusions:

• Pathogenic variants in EXOC2 are a cause of severe neurological disorders.
• Disruption of exocyst function through EXOC2 mutations impacts neural development.
• EXOC2 mutations provide insights into the essential role of the exocyst complex in neuronal function.