MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II.

@article{Pannu2007MYH11MR,
  title={MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II.},
  author={H. Pannu and V. Tran-Fadulu and Christina L. Papke and Steve Scherer and Yaozhong Liu and C. Presley and D. Guo and A. Estrera and H. Safi and A. Brasier and G. W. Vick and A. Marian and C. Raman and L. Buja and D. Milewicz},
  journal={Human molecular genetics},
  year={2007},
  volume={16 20},
  pages={
          2453-62
        }
}
Non-syndromic thoracic aortic aneurysms and dissections (TAADs) are inherited in an autosomal dominant manner in approximately 20% of cases. Familial TAAD is genetically heterogeneous and four loci have been mapped for this disease to date, including a locus at 16p for TAAD associated with patent ductus arteriosus (PDA). The defective gene at the 16p locus has recently been identified as the smooth muscle cell (SMC)-specific myosin heavy chain gene (MYH11). On sequencing MYH11 in 93 families… Expand
Novel MYH11 and ACTA2 mutations reveal a role for enhanced TGFβ signaling in FTAAD.
TLDR
Interestingly, immunohistochemical staining of aortic biopsies of a patient and a family member with MYH11 and patients with ACTA2 missense mutations showed upregulation of the TGFβ signaling pathway. Expand
Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections
TLDR
It is suggested that ACTA2 should be included in the genes routinely investigated for syndromic and nonsyndromic TAAD and underscore the role ofACTA2 mutations in nonsyNDromicTAAD. Expand
Incomplete segregation of MYH11 variants with thoracic aortic aneurysms and dissections and patent ductus arteriosus
TLDR
It is concluded that in familial TAAD/PDA with an MYH11 variant in the index case caution should be exercised upon counseling family members, and that segregation analysis remains very important in clinical genetics. Expand
Genetic basis of thoracic aortic aneurysms and dissections: focus on smooth muscle cell contractile dysfunction.
TLDR
The recent discovery that mutations in the vascular smooth muscle cell (SMC)-specific beta-myosin (MYH11) and alpha-actin (ACTA2) can also cause this disorder has focused attention on the importance of the maintenance of SMC contractile function in preserving aortic structure and preventing TAAD. Expand
Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections.
TLDR
Identification of a gain-of-function mutation in PRKG1 as a cause of thoracic aortic disease provides further evidence that proper SMC contractile function is critical for maintaining the integrity of the thoracIC aorta throughout a lifetime. Expand
ACTA2 is not a major disease-causing gene for moyamoya disease
TLDR
The finding of another patient with TAAD and premature stroke in family TAA377 also indicated premature early stage of MMD, because MMD can be diagnosed when patients showed clinical symptoms derived from neurovascular involvements and their radiographic findings revealed moyamoya vessels as the collateral arteries caused by the stenosis of the region of middle cerebral arteries. Expand
Mutations in myosin light chain kinase cause familial aortic dissections.
TLDR
Genetic and functional studies support the conclusion that heterozygous loss-of-function mutations in MYLK are associated with aortic dissections and mice with SMC-specific knockdown of Mylk demonstrate altered gene expression and pathology consistent with medial degeneration of the aorta. Expand
Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD)
TLDR
It is confirmed that ACTA2 mutations are important in familial TAAD, while the first sporadic and young‐onset TAAD case with an ACTA 2 mutation was also identified. Expand
Protein‐elongating mutations in MYH11 are implicated in a dominantly inherited smooth muscle dysmotility syndrome with severe esophageal, gastric, and intestinal disease
TLDR
It is hypothesized that the mechanistic pathogenesis of this disease, dominant hypercontractile loss‐of‐function, is distinct from those implicated in other diseases involving MYH11 dysfunction. Expand
A new Variant in the MYH11 gene in a Familial case of Thoracic Aortic Aneurysm.
TLDR
A rare missense variant in the MYH11 gene predicted to be damaging and affecting a conserved amino-acid in the myosin tail of the protein appears to be responsible for the familial case of TAA, as the clinical expression reunited all features of genetic aneurysms. Expand
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