Cytoskeleton is made up of different types of proteins and is the overall scaffold of the cells. It is responsible for cell division and movement and thus important for organ formation. Actin cytoskeleton is a subset of the overall cytoskeleton. A group of proteins, the Rho family of GTPases (including Cdc42 and Rac1), is a part of a control mechanism for actin cytoskeleton. The Rho family of GTPases are in turn regulated by other groups of proteins, including ARHGAP31 and DOCK6 .
A 2011 study identifies an ARHGAP31 mutation as the cause of autosomal dominant AOS . The mutation makes ARHGAP31 proteins more active, disrupting the cytoskeletal structure through the inappropriate interaction with Cdc42/Rac1. Study of ARHGAP31 in mouse model, however, shows that this mutation cannot explain the occurrence of congenital cardiac abnormalities in some AOS individuals . Future study may identify other mutations for AOS with different clinical features.
Researchers in a later study identify a DOCK6 gene mutation in one patient and confirm the finding in a second patient. Interestingly, DOCK6 protein also regulates Cdc42 and Rac1 .
These two studies suggest that inactivation of Cdc42 and Rac1 is a common pathway that lead to abnormal actin cytoskeleton organization. Further studies should be done to examine other regulators of proteins in the Rho family of GTPases . Studies to identify gene mutations can help us better categorize AOS into different subsets and to understand the pathology, ultimately leading to more effective management of AOS.
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