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Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD)

Published on Oct 1, 2009in Human Mutation4.45
· DOI :10.1002/humu.21081
Hiroko Morisaki23
Estimated H-index: 23
,
Koichi Akutsu14
Estimated H-index: 14
+ 11 AuthorsTakayuki Morisaki31
Estimated H-index: 31
(Osaka University)
Cite
Abstract
Approximately 20% of aortic aneurysm and/or dissection (AAD) cases result from inherited disorders, including several systemic and syndromatic connective-tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, which are caused by mutations in the FBN1, COL3A1, and TGFBR1 and TGFBR2 genes, respectively. Nonsyndromatic AAD also has a familial background, and mutations of the ACTA2 gene were recently shown to cause familial AAD. In the present study, we conducted sequence analyses of the ACTA2 gene in 14 unrelated Japanese patients with familial thoracic AAD (TAAD), and in 26 with sporadic and young-onset TAAD. Our results identified three mutations of ACTA2, two novel [p.G152_T205del (c.616+1G>T), p.R212Q] and one reported (p.R149C), in the 14 patients with familial TAAD, and a novel mutation (p.Y145C) of ACTA2 in the 26 sporadic and young-onset TAAD patients, each of which are considered to be causative for TAAD. Some of the clinical features of these patients were the same as previously reported, whereas others were different. These findings confirm that ACTA2 mutations are important in familial TAAD, while the first sporadic and young-onset TAAD case with an ACTA2 mutation was also identified. Hum Mutat 30:1–6, 2009. © 2009 Wiley-Liss, Inc.
  • References (21)
  • Citations (59)
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References21
Newest
Published on May 1, 2009in American Journal of Human Genetics9.92
Dongchuan Guo32
Estimated H-index: 32
(University of Texas Health Science Center at Houston),
Christina L. Papke9
Estimated H-index: 9
(University of Texas Health Science Center at Houston)
+ 28 AuthorsElizabeth Sparks21
Estimated H-index: 21
(Harvard University)
The vascular smooth muscle cell (SMC)-specific isoform of α-actin (ACTA2) is a major component of the contractile apparatus in SMCs located throughout the arterial system. Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections (TAAD), but only half of mutation carriers have aortic disease. 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 p...
Published on Dec 1, 2007in Nature Genetics25.45
Dongchuan Guo32
Estimated H-index: 32
(University of Texas Health Science Center at Houston),
Hariyadarshi Pannu18
Estimated H-index: 18
(University of Texas Health Science Center at Houston)
+ 22 AuthorsElizabeth Sparks21
Estimated H-index: 21
(OSU: Ohio State University)
Mutations in smooth muscle α-actin ( ACTA2 ) lead to thoracic aortic aneurysms and dissections
Published on Sep 1, 2007in American Journal of Human Genetics9.92
Laurence Faivre50
Estimated H-index: 50
,
Gwenaëlle Collod-Béroud27
Estimated H-index: 27
(University of Montpellier)
+ 29 AuthorsMine Arslan-Kirchner14
Estimated H-index: 14
(MHH: Hannover Medical School)
Mutations in the fibrillin-1 (FBN1) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes. Clinical care is complicated by variable age at onset and the wide range of severity of aortic features. The factors that modulate phenotypical severity, both among and within families, remain to be determined. The availability of international FBN1 mutation Universal Mutation Database (UMD-FBN1) has allowed us to perform the largest collaborative study ever ...
Published on Apr 5, 2007in Human Molecular Genetics4.54
Hariyadarshi Pannu18
Estimated H-index: 18
,
Van Tran-Fadulu11
Estimated H-index: 11
+ 12 AuthorsAllan R. Brasier54
Estimated H-index: 54
(UTMB: University of Texas Medical Branch)
Non-syndromic thoracic aortic aneurysms and dissections (TAADs) are inherited in an autosomal dominant manner in 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 with TAAD alone a...
Published on Nov 1, 2006in Annals of the New York Academy of Sciences4.29
Hariyadarshi Pannu18
Estimated H-index: 18
(University of Texas Health Science Center at Houston),
Nili Avidan21
Estimated H-index: 21
(University of Texas Health Science Center at Houston)
+ 1 AuthorsDianna M. Milewicz56
Estimated H-index: 56
(University of Texas Health Science Center at Houston)
: Ascending thoracic aortic aneurysms leading to type A dissections (TAAD) have long been known to occur in association with a genetic syndrome such as Marfan syndrome (MFS). More recently, TAAD has also been demonstrated to occur as an autosomal dominant disorder in the absence of syndromic features, termed familial TAAD. Familial TAAD demonstrates genetic heterogeneity, and linkage studies have identified TAAD loci at 5q13-14 (TAAD1), 11q23 (FAA1), 3p24-25 (TAAD2), and 16p12.2-13.13. The genet...
Published on Oct 1, 2006in The Annals of Thoracic Surgery3.92
Gonzalo Albornoz3
Estimated H-index: 3
(Yale University),
Michael A. Coady23
Estimated H-index: 23
(Yale University)
+ 4 AuthorsJohn A. Elefteriades54
Estimated H-index: 54
(Yale University)
Background We examined the genetic nature and phenotypic features of thoracic aortic aneurysms (TAAs) and dissections in a large cohort of patients. Methods Interviews were conducted with 520 patients with TAAs and their pedigrees were compiled to identify family members with aneurysms. Study patients were divided into three groups: 101 non-Marfan patients, in 88 pedigrees, had a family pattern for TAA (familial group), 369 had no family pattern (sporadic group), and 50 had Marfan syndrome (MFS)...
Published on Mar 1, 2006in Nature Genetics25.45
Limin Zhu5
Estimated H-index: 5
,
Roger Vranckx24
Estimated H-index: 24
+ 11 AuthorsFrançois Brunotte28
Estimated H-index: 28
Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus
Published on Sep 1, 2005in Nature43.07
Vidu Garg25
Estimated H-index: 25
(UTSW: University of Texas Southwestern Medical Center),
Alecia N. Muth4
Estimated H-index: 4
(UCSF: University of California, San Francisco)
+ 5 AuthorsDeepak Srivastava78
Estimated H-index: 78
A genetic basis for aortic valve calcification, a leading cause of heart disease in adults, has been discovered in a study of congenital heart disease in five generations of the same family. The disease was apparent in family members with a mutation in the transcriptional regulator NOTCH1. The mutant gene causes heart valve defects in transgenic mice. NOTCH1 mutations have previously been identified in human blood cancers, but this is the first indication that it has a role in the development of...
Published on Mar 1, 2005in Nature Genetics25.45
Bart Loeys56
Estimated H-index: 56
(Johns Hopkins University),
Junji Chen1
Estimated H-index: 1
(Johns Hopkins University)
+ 21 AuthorsNeda Sharifi2
Estimated H-index: 2
(Johns Hopkins University)
We report heterozygous mutations in the genes encoding either type I or type II transforming growth factor β receptor in ten families with a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development. Despite evidence that receptors derived from selected mutated alleles cannot support TGFβ signal propagation, cells derived from individuals heterozygous with respect to these mutations did not show altered kinetic...
Published on Nov 1, 2004in Trends in Biochemical Sciences16.89
Roberto Dominguez37
Estimated H-index: 37
(Boston Biomedical Research Institute)
Actin participates in more protein–protein interactions than any other known protein, including the interaction of actin with itself to form the helical polymer F-actin. The vast majority of actin-binding proteins (ABPs) can be grouped into conserved families. Only a handful of structures of complexes of actin with ABPs have been determined so far. These structures are starting to reveal how certain ABPs, including gelsolin, vitamin D-binding protein and Wiskott–Aldrich syndrome protein (WASP)-h...
Cited By59
Newest
Published on Feb 11, 2019in Genetics in Medicine8.68
Pauline Arnaud4
Estimated H-index: 4
(Paris Diderot University),
Nadine Hanna10
Estimated H-index: 10
(Paris Diderot University)
+ 19 AuthorsThomas Edouard7
Estimated H-index: 7
Heritable thoracic aortic aneurysms and dissections (hTAAD) are life-threatening complications of well-known syndromic diseases or underdiagnosed nonsyndromic heritable forms (nshTAAD). Both have an autosomal dominant transmission and are genetically heterogeneous. Our objective was to describe the relevance of molecular diagnosis in these patients and the contribution of each gene in nshTAAD. Two hundred twenty-six consecutive nshTAAD probands, either young (<45 years) sporadic or familial case...
Published on Nov 20, 2018in Clinical Infectious Diseases9.05
Jayant V. Rajan6
Estimated H-index: 6
(UCSF: University of California, San Francisco),
Fred Semitala10
Estimated H-index: 10
(MUK: Makerere University)
+ 10 AuthorsSandra Mwebe3
Estimated H-index: 3
Adam J. Brownstein4
Estimated H-index: 4
(Yale University),
Bulat A. Ziganshin14
Estimated H-index: 14
(Yale University),
John A. Elefteriades54
Estimated H-index: 54
(Yale University)
Thoracic aortic aneurysm (TAA), a typically silent but frequently lethal disease, is strongly influenced by underlying genetics. Approximately 30 genes have been associated with syndromic and non-syndromic familial thoracic aortic aneurysm and dissection (TAAD) to date. An estimated 30% of patients with non-syndromic familial TAAD, which is typically inherited in an autosomal dominant manner, have a mutation in one of these genes. The underlying genetic mutation helps predict patients’ clinical ...
We discuss the etiology of aortic dissection (AD) from various points of view. The development of AD requires two pathological conditions: medial degeneration and mechanical wall stress. First, histopathological findings of medial degeneration are hypothesized to be due to a loss of elastic fibers and interconnecting elastic fibers. Damage to the vasa vasorum plays a key role in creating an entry site. The clinical causes of medial degeneration include hypertension, aortic aneurysms, obstructive...
Published on Dec 1, 2018in BMC Medical Genetics1.74
Anna Keravnou4
Estimated H-index: 4
(The Cyprus Institute of Neurology and Genetics),
Evy Bashiardes6
Estimated H-index: 6
(The Cyprus Institute of Neurology and Genetics)
+ 3 AuthorsMarios A. Cariolou18
Estimated H-index: 18
(The Cyprus Institute of Neurology and Genetics)
Thoracic aortic aneurysm (TAA) and/or thoracic aortic aneurysm and dissection (TAAD) is characterized by a considerable risk of morbidity and mortality of affected individuals. It is inherited in an autosomal dominant pattern and the 20% of patients with non-syndromic TAA have a positive family history. To date, the genetic basis of Cypriot patients with TAA has not been investigated. The purpose of this case report is to determine underlying genetic cause in this Cypriot family with TAA. In thi...
Published on Jan 1, 2018
Marie-Catherine Morgant1
Estimated H-index: 1
(MHI: Montreal Heart Institute),
Ismail El-Hamamsy23
Estimated H-index: 23
(MHI: Montreal Heart Institute)
Heritable connective tissue diseases comprise a heterogeneous group of multi-systemic disorders that result from genetic defects affecting normal extracellular matrix (ECM) assembly and maintenance. The connective tissue is a tissue structure which represents a three-dimensional thread. The three main functions of connective tissues are support, protection, and nutrition of other tissues. It is mainly the support function which is affected in pathologies discussed in this chapter. Connective tis...
Published on Dec 1, 2017in Journal of Cardiothoracic Surgery1.47
Toshiki Fujiyoshi2
Estimated H-index: 2
(TMU: Tokyo Medical University),
Kenji Minatoya26
Estimated H-index: 26
+ 4 AuthorsHitoshi Ogino25
Estimated H-index: 25
(TMU: Tokyo Medical University)
A retrospective analysis was performed to determine the impact of genetically diagnosed connective tissue disease (CTD) on the early and late outcomes of surgical treatment for aortic dissection in patients having aortic pathology associated with cystic medial necrosis (CMN). Between 2003 and 2013, a total of 43 patients (37 ± 12.8 years old, 23 men, 20 women) who had undergone surgery for aortic dissection associated with CMN in the aortic wall underwent genetic examinations. Subsequently, ther...
Published on Dec 1, 2017in Scientific Reports4.01
Miaoxian Fang1
Estimated H-index: 1
(Academy of Medical Sciences, United Kingdom),
Changjiang Yu1
Estimated H-index: 1
(Academy of Medical Sciences, United Kingdom)
+ 5 AuthorsRuixin Fan1
Estimated H-index: 1
(Academy of Medical Sciences, United Kingdom)
Thoracic Aortic Aneurysm and Dissection (TAAD) is a life-threatening pathology and remains challenging worldwide. Up to 40% of TAAD are hereditary with complex heterogeneous genetic backgrounds. Recently, next-generation sequencing (NGS) has been successfully applied to identify genetic variants in an efficient and cost-effective manner. In our study, NGS coupled with DNA target-capture array was used to screen 11 known causative genes of TAAD in 70 patients from Southern China. All the identifi...
Yoshimasa Seike6
Estimated H-index: 6
,
Kenji Minatoya26
Estimated H-index: 26
+ 7 AuthorsJunjiro Kobayashi35
Estimated H-index: 35
Objectives Actin, alpha-2, smooth muscle, aorta (ACTA2) mutations are one of the major causes of familial thoracic aortic aneurysms and dissections. The aim of this study was to review our clinical results of young adult patients with aortic disease caused by ACTA2 mutations.