In addition to showing that extracranial AVMs demonstrate interrupted elastin and that AVMs and LMs demonstrate abnormal α-smooth muscle actin just as brain AVMS do, our results demonstrate that NOTCH1, 2, 3 and 4 proteins are overexpressed to varying degrees in both the endothelial and mural lining of the malformed vessels in all types of malformations.
Injection of the WHD2-deleted mutant into oocytes caused a drastic accumulation of actin filaments in the cytoplasm and malformation of MTOC-TMA, suggesting that the WHD2 domain negatively regulates the VCA domain activity during oocyte maturation.
We describe heterozygous ACTB deletions and nonsense and frameshift mutations in 33 individuals with developmental delay, apparent intellectual disability, increased frequency of internal organ malformations (including those of the heart and the renal tract), growth retardation, and a recognizable facial gestalt (interrupted wavy eyebrows, dense eyelashes, wide nose, wide mouth, and a prominent chin) that is distinct from characteristics of individuals with BRWS.
However, several patients with Fryns-Aftimos were considered not to fit into the ACTB and ACTG1 spectrum because of their severe impairment and additional malformations.
A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia.