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A novel variant in MYLK causes thoracic aortic dissections : genotypic and phenotypic description

Published on Dec 1, 2016in BMC Medical Genetics1.74
· DOI :10.1186/s12881-016-0326-y
Matias Hannuksela3
Estimated H-index: 3
(Umeå University),
Eva-Lena Stattin17
Estimated H-index: 17
(Umeå University)
+ 4 AuthorsBo Carlberg29
Estimated H-index: 29
(Umeå University)
Abstract
Background: Mutations in MYLK cause non- syndromic familial thoracic aortic aneurysms and dissections (FTAAD). Very little is known about the phenotype of affected families. We sought to characteri ...
  • References (30)
  • Citations (10)
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References30
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#1Sue Richards (OHSU: Oregon Health & Science University)H-Index: 5
#2Nazneen Aziz (Boston Children's Hospital)H-Index: 6
Last. Heidi L. Rehm (Harvard University)H-Index: 51
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Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology
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#1Ellen S. Regalado (University of Texas Health Science Center at Houston)H-Index: 25
#2Dongchuan Guo (University of Texas Health Science Center at Houston)H-Index: 33
Last. Dianna M. Milewicz (University of Texas Health Science Center at Houston)H-Index: 58
view all 21 authors...
Background— ACTA2 mutations are the major cause of familial thoracic aortic aneurysms and dissections. We sought to characterize these aortic diseases in a large case series of individuals with ACTA2 mutations. Methods and Results— Aortic disease, management, and outcome associated with the first aortic event (aortic dissection or aneurysm repair) were abstracted from the medical records of 277 individuals with 41 various ACTA2 mutations. Aortic events occurred in 48% of these individuals, with ...
44 CitationsSource
#1Adam Ameur (Science for Life Laboratory)H-Index: 23
#2Ignas Bunikis (Science for Life Laboratory)H-Index: 6
Last. Ulf Gyllensten (Science for Life Laboratory)H-Index: 80
view all 4 authors...
CanvasDB is an infrastructure for management and analysis of genetic variants from massively parallel sequencing (MPS) projects. The system stores SNP and indel calls in a local database, designed to handle very large datasets, to allow for rapid analysis using simple commands in R. Functional annotations are included in the system, making it suitable for direct identification of disease-causing mutations in human exome- (WES) or whole-genome sequencing (WGS) projects. The system has a built-in ...
14 CitationsSource
#1Jana Marie Schwarz (Charité)H-Index: 6
#2David Neil Cooper (Cardiff University)H-Index: 92
Last. Dominik Seelow (Charité)H-Index: 21
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#1Bartosz Rylski (University of Freiburg)H-Index: 18
#2Philipp BlankeH-Index: 40
Last. Joseph E. Bavaria (HUP: Hospital of the University of Pennsylvania)H-Index: 64
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OBJECTIVES The purpose of this study is to delineate changes in aortic geometry and diameter due to dissection. BACKGROUND Aortic diameter is the major criterion for elective ascending aortic replacement for dilated ascending aortas to prevent aortic dissection. However, recommendations are made on the basis of clinical experience and observation of diameters of previously dissected aortas. METHODS Six tertiary centers on 2 continents reviewed their acute aortic dissection type A databases, whic...
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#1Anne E Davis (John Radcliffe Hospital)H-Index: 1
#2Adam J. Lewandowski (University of Oxford)H-Index: 21
Last. Oliver J. Rider (John Radcliffe Hospital)H-Index: 21
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Background Cardiovascular magnetic resonance (CMR) is regarded as the gold standard for clinical assessment of the aorta, but normal dimensions are usually referenced to echocardiographic and computed tomography data and no large CMR normal reference range exists. As a result we aimed to 1) produce a normal CMR reference range of aortic diameters and 2) investigate the relationship between regional aortic size and body surface area (BSA) in a large group of healthy subjects with no vascular risk...
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#1Elisabeth GillisH-Index: 5
#2Lut Van LaerH-Index: 39
Last. Bart LoeysH-Index: 56
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Aortic aneurysm, including both abdominal aortic aneurysm and thoracic aortic aneurysm, is the cause of death of 1% to 2% of the Western population. This review focuses only on thoracic aortic aneurysms and dissections. During the past decade, the genetic contribution to the pathogenesis of thoracic aortic aneurysms and dissections has revealed perturbed extracellular matrix signaling cascade interactions and deficient intracellular components of the smooth muscle contractile apparatus as the ke...
102 CitationsSource
#1Pawel Pomianowski (Yale University)H-Index: 4
#2John A. Elefteriades (Yale University)H-Index: 55
Genetic studies over the past several decades have helped to better elucidate the genomics and inheritance of thoracic aortic diseases. Seminal work from various researchers have identified several genetic factors and mutations that predispose to aortic aneurysms, which will aid in better screening and early intervention, resulting in better clinical outcomes. Syndromic aneurysms have been associated with Marfan syndrome, Loeys-Dietz syndrome, aneurysm osteoarthritis syndrome, arterial tortuosit...
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Background Aortic size is known to vary significantly by age and body size and to be an important predictor of cardiovascular diseases. The aim of this study was to determine reference values for proximal thoracic aorta diameters, using the inner edge technique and two-dimensional transthoracic echocardiography. Methods Diameters of the aortic annulus, sinuses of Valsalva, sinotubular junction, arch, and ascending aorta and the angle of insertion of the aorta were measured in 500 subjects (231 w...
35 CitationsSource
#2Gonçalo R. Abecasis (UM: University of Michigan)H-Index: 144
#3Adam Auton (Yeshiva University)H-Index: 36
Last. Gilean McVean (University of Oxford)H-Index: 80
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By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million si...
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Aortic aneurysms were the primary cause of nearly 10,000 deaths in 2014 according to data from the Centers for Disease Control and may involve segments of the thoracic or abdominal aorta. Thoracic ...
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#1Stephanie E. Wallace (University of Texas Health Science Center at Houston)H-Index: 3
#2Ellen S. Regalado (University of Texas Health Science Center at Houston)H-Index: 25
Last. Dianna M. Milewicz (University of Texas Health Science Center at Houston)H-Index: 58
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Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLK missense variants are pathogenic and information to guide aortic disease management are limited. Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed. Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm rep...
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#2Raymond A. DieterJr. (NU: Northwestern University)
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The clinically most important aortic diseases are those that cause aneurysms and dissections in the aortic wall. Aortic aneurysms and/or dissections are sometimes subject to sudden rupture, which often causes sudden death. Currently the biggest problem in addressing sudden rupture is, that early stage aneurysm, which can be successfully treated by surgery, remains often undetected because it is not associated with clearly detectable symptoms.
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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...
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#1Lifei Wu (Shanxi Medical University)
Abstract Thoracic aortic aneurysm is extremely threatening due to high risk of dissection and rupture. Genetic factors play decisive role in the pathogenesis of thoracic aortic aneurysm. Recent years, several genes are considered to be associated with thoracic aortic aneurysm, among these genes, 11 gene variants identified are responsible for thoracic aortic aneurysm. In this review, we mainly discussed the function of the 11 gene variants in thoracic aortic aneurysm and the histology and cytoki...
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Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital disorder characterized by loss of smooth muscle contraction in the bladder and intestine. To date, three genes are known to be involved in MMIHS pathogenesis: ACTG2, MYH11, and LMOD1. However, for approximately 10% of affected individuals, the genetic cause of the disease is unknown, suggesting that other loci are most likely involved. Here, we report on three MMIHS-affected subjects from two consanguineous familie...
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