ACTA2

Congenital mydriasis was associated with the R179 mutation in the cases that tested positive for ACTA2 mutation.

ACTA2-related diseases can be inherited in an autosomal dominant manner, meaning that a single copy of the pathogenic variant is sufficient to cause the condition. However, de novo (sporadic) variants can also occur, meaning they arise in an affected individual without being inherited from their parents.

Yes, research is actively being conducted to further understand the molecular mechanisms underlying ACTA2-related diseases and to explore potential therapeutic strategies. This includes investigating the specific effects of different pathogenic variants and developing animal models to study the disease progression and test potential treatments.

ACTA2 variants altering arginine 179 are associated with a more severe, multisystemic disease called smooth muscle dysfunction syndrome (SMDS). This syndrome involves dysfunction of smooth muscle-dependent systems in various parts of the body.

Pathogenic variants in ACTA2 can disrupt the normal structure or function of smooth muscle α-actin. This can lead to smooth muscle dysfunction, affecting various systems in the body, particularly the vascular system. The altered actin protein may impair smooth muscle contraction, leading to abnormalities such as thoracic aortic aneurysms and dissections.

Currently, there is no cure for ACTA2-related conditions. Treatment focuses on managing symptoms and preventing complications. This may involve surgical interventions to repair or replace affected blood vessels, medication to control blood pressure, and regular monitoring of cardiovascular health.

The lifetime risk for an aortic event in individuals with ACTA2 mutations is reported to be 76%. This indicates that a significant proportion of individuals with these mutations will experience an aortic event at some point in their lifetime.

The cell assays showed that ACTA2 overexpression led to decreased cell proliferation, migration, invasion, and angiogenic ability in the HMEC-1 model.

 ACTA2 knockdown in the zebrafish model resulted in defective vascular development, disruption of vascular integrity, and malformation of micro vein development.

The expression of ACTA2 in the pathological tissues of patients with venous malformations and control tissues was detected using both quantitative polymerase chain reaction (qPCR) and western blot techniques.

ACTA2 mutations are associated with a high risk of presentation with an acute aortic dissection. These mutations increase the likelihood of developing this serious condition.

No, in this series, ACTA2 mutations or copy number variations were not detected in children presenting with iris flocculi.

Mutations or alterations in the ACTA2 gene can disrupt the normal structure or function of smooth muscle α-actin. This can lead to smooth muscle dysfunction and contribute to the development of various diseases, particularly those affecting the vascular system.

Pathogenic variants in ACTA2, which encodes smooth muscle α-actin, predispose individuals to thoracic aortic aneurysms and dissections. These variants contribute to the development of these cardiovascular conditions.

 In addition to thoracic aortic disease, pathogenic ACTA2 variants are also associated with various vascular complications, including arterial aneurysms in other parts of the body, arterial tortuosity, and early-onset ischemic strokes. Other non-vascular manifestations can include ocular abnormalities, such as iris flocculi and congenital mydriasis, as well as genitourinary and gastrointestinal issues.

The clinical presentations of the patients with the novel heterozygous ACTA2 missense variants include a range of complications that align or overlap with SMDS. These complications can affect various body systems and may differ among individuals with different variants.

ACTA2 encodes smooth muscle α-actin, which is involved in the contraction and maintenance of smooth muscle cells. It plays a crucial role in the function of various organs and tissues, including blood vessels, airways, and the gastrointestinal tract.

ACTA2 is a gene that encodes for smooth muscle α-actin, a protein involved in the contraction and maintenance of smooth muscle cells.

ACTA2 is found in various smooth muscle tissues throughout the body, including blood vessels, airways, the gastrointestinal tract, and other organs.

The knockdown of ACTA2 inhibited the Dll4/notch1 signaling pathway, Ephrin-B2 signaling pathway, and affected vascular integrity-related molecules. It also activated the Hedgehog signaling pathway.

Yes, there are unusual vascular complications observed in some patients with other ACTA2 missense variants. For example, the patient with the ACTA2 p.Ile66Asn variant has a large fusiform internal carotid artery aneurysm, which is an atypical vascular complication. Similarly, the patient with the ACTA2 p.Arg39Cys variant has complications in the pulmonary, gastrointestinal, and genitourinary systems, but no vascular manifestations