CDC42 missense mutations and human diseases: from neurodevelopmental disorders to autoinflammation

Area of Science:

• Molecular Biology
• Immunology
• Genetics

Background:

• Cdc42, a Rho family GTPase, regulates cellular functions via numerous protein interactions.
• Genomic studies link Cdc42 variants to pathological conditions, including severe autoinflammation.
• This highlights a previously unrecognized role for Cdc42 in innate immunity.

Purpose of the Study:

• To review current knowledge on CDC42 mutations in human diseases.
• To focus on early-onset autoinflammation linked to carboxyl-terminal Cdc42 mutations.
• To explore the implications for innate immunity and therapeutic strategies.

Main Methods:

• Literature review of genomic analyses and clinical studies.
• Analysis of reported pathological phenotypes associated with Cdc42 variants.
• Synthesis of information on Cdc42's role in inflammatory pathways.

Main Results:

• Cdc42 missense variants are associated with diverse pathological phenotypes.
• Specific mutations, particularly at the carboxyl-terminus, are implicated in severe autoinflammation.
• These findings underscore Cdc42's critical involvement in innate immune responses.

Conclusions:

• CDC42 mutations contribute to human diseases, notably early-onset autoinflammation.
• Further research is needed to fully understand Cdc42-induced inflammatory mechanisms.
• Targeting Cdc42 pathways may offer novel therapeutic avenues for inflammatory disorders.