Molecular pathology of filamin A: diverse phenotypes, many functions

Abstract

Defective cell signalling during embryonic development is a well-recognized modus operandi of mutations in genes that lead to congenital malformations. This signalling occurs within and around a dynamic cellular cytoskeleton that is continuously under modulating influences during morphogenesis. Evidence is accumulating to suggest that filamin A, an actin-binding protein and the product of one of three paralogous filamin genes in humans, represents a key molecule that connects such signalling events to modulation of the cellular cytoskeletal architecture. This review summarizes the clinical consequences of mutations in the gene encoding filamin A, FLNA. The molecular pathology of this gene suggests remarkable functional pleiotropy, indicative of diverse roles in embryonic, fetal and postnatal development.