ACTA2 mutations are recently described genetically defined abnormalities of blood vessels in various organs of the body with specific abnormalities in cerebral vessels in the form of straightening of all cerebral arteries ("twig-like" pattern), stenosis/occlusions, proximal dilatation, and absent "moyamoya" type of collaterals.
However, recent basic science and clinical data have demonstrated that the cerebral arteriopathy caused by mutant ACTA2 exhibits genetic loci, histopathology, neurological sequelae, and radiographic findings unique from moyamoya disease.
Mutations in ACTA2 are the most common genetic cause of thoracic aortic aneurysm, and are also the cause of other disorders, including Moyamoya disease, coronary artery disease and stroke as well as Multisystemic Smooth Muscle Dysfunction Syndrome.
Concurrent cardio- and cerebrovascular lesions have been reported in PHACE syndrome, ACTA2 mutation syndrome, and less frequently in the spontaneous occlusion of the circle of Willis (so-called moyamoya disease).
The authors conducted a genetic study of really interesting new gene (RING) finger protein 213 ( RNF213); actin alpha 2 ( ACTA2); BRCA1/BRCA2-containing complex subunit 3 ( BRCC3); and guanylate cyclase 1, soluble, alpha 3 ( GUCY1A3) as well as a clinical phenotype analysis in Chinese MMD patients to determine whether genetic differences are responsible for the different clinical features that appear in MMD in different ethnicities.
While direct cerebrovascular bypass is technically feasible, patients with ACTA2 arteriopathy may be at increased risk for perioperative stroke compared with patients with moyamoya disease.
Mutations in the smooth muscle-specific isoform of α-actin (ACTA2) cause vascular smooth muscle dysfunction leading to aortic aneurysm and moyamoya syndrome.
Further combined analysis of ACTA2 and other, possibly causative, genes in larger cohorts of MMD and other vascular diseases may identify possible common disease-causing mechanisms.
Further combined analysis of ACTA2 and other, possibly causative, genes in larger cohorts of MMD and other vascular diseases may identify possible common disease-causing mechanisms.
Investigations included neuroimaging, cardiologic and ophthalmologic evaluation, hormonal testing, hemoglobin electrophoresis, chromosomal karyotyping, muscle biopsy for morphology, immunohistochemistry and enzyme assays, mtDNA mutation screening, and haplotype analysis of 2 loci previously linked to moyamoya, on chromosomes 10 (ACTA2) and 17.
Linkage analysis and association studies of individuals in 20 families with ACTA2 mutations indicate that mutation carriers can have a diversity of vascular diseases, including premature onset of coronary artery disease (CAD) and premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD.
Linkage analysis and association studies of individuals in 20 families with ACTA2 mutations indicate that mutation carriers can have a diversity of vascular diseases, including premature onset of coronary artery disease (CAD) and premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD.
Though her 2 children and uncle had a typical moyamoya disease with RNF213p.R4810K heterozygous variant, she has had no clinical and radiological evidence of moyamoya disease.
Mutations in Ring Finger Protein 213 (<i>RNF213</i>), a Zinc ring finger protein, have been identified in some MMD patients but the etiology of MMD is still largely unknown.
Two MMD-associated rare variants (p.R4810K and p.A4399T) in RNF213 were identified in two patients, three BMPR2 mutations (p.Q92H, p.L198Rfs*4, and p.S930X) were found in three patients, whereas no CAV1 mutations were identified.
Background and Purpose- The ring finger protein 213 gene ( RNF213) is a susceptibility gene for moyamoya disease and large-artery ischemic stroke in East Asia.
On the other hand, a common missense mutation [NM_001256071.2:c.14429G>A (p.Arg4810Lys)] related to MMD in exon 60 of RNF213 was also identified by Sanger sequencing.