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Article
Open AccessExpanding the clinical spectrum of biglycan-related Meester-Loeys syndrome
Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of...
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Article
Open AccessGenetic association analysis of 77,539 genomes reveals rare disease etiologies
The genetic etiologies of more than half of rare diseases remain unknown. Standardized genome sequencing and phenoty** of large patient cohorts provide an opportunity for discovering the unknown etiologies, ...
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Pathophysiology and Principles of Management of Hereditary Aneurysmal Aortopathies
Aortic aneurysm refers to a pathological dilatation of the aorta and predisposes to rupture and dissection. It is an important health problem, accounting for 1–2% of all deaths in the Western population. Thora...
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Article
ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm
Bicuspid aortic valve (BAV) is a common congenital heart defect (population incidence, 1–2%)1–3 that frequently presents with ascending aortic aneurysm (AscAA)4. BAV/AscAA shows autosomal dominant inheritance wit...
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Article
Correction: Corrigendum: SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome
Nat. Genet. 49, 238–248 (2017); published online 9 January 2017; corrected after print 20 March 2017 In the version of this article initially published, the legend to Figure 4c stated that only one proband wit...
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Article
SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome
Michael Talkowski, David FitzPatrick, Erica Davis and colleagues report rare inherited or de novo missense variants in SMCHD1 in arhinia patients. Some of the same mutations in SMCHD1 are known to cause a phenoty...
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Open AccessEducational paper
Heritable connective tissue diseases comprise a heterogeneous group of multisystemic disorders that are characterized by significant morbidity and mortality. These disorders do not merely result from defects i...
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Article
Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm
Harry Dietz and colleagues report the identification of mutations in SKI in Shprintzen-Goldberg syndrome, which shares features with Marfan syndrome and Loeys-Dietz syndrome. SKI encodes a known repressor of TGF-...
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Article
Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm
Bart Loeys and colleagues identify mutations or deletions of TGFB2 in individuals with thoracic aortic aneurysm and other features of Loeys-Dietz syndrome. TGFB2 encodes the transforming growth factor-β2 ligand.
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Article
The diagnostic value of the facial features of Marfan syndrome
We examined the prevalence of known facial features of Marfan syndrome (MFS)—dolicocephaly, malar hypoplasia, enophthalmos, retrognathia, and down-slanting palpebral fissures—and the diagnostic utility (sensit...
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Article
New insights into the pathogenesis and treatment of arterial aneurysms and dissections
Aortic aneurysm and dissection (AAD) is a common cause of morbidity and death in the Western world. Over the last decade tremendous progress has been made in the identification of the genetic basis of aortic a...
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Article
Correction: Corrigendum: Angiotensin II type 1 receptor blockade attenuates TGF-β–induced failure of muscle regeneration in multiple myopathic states
Nat. Med. 12, 204–210 (2007); published online 21 January 2007; corrected after print 27 February 2007 In the version of this article initially published, the same panels were inadvertently used to show negati...
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Article
Angiotensin II type 1 receptor blockade attenuates TGF-β–induced failure of muscle regeneration in multiple myopathic states
Skeletal muscle has the ability to achieve rapid repair in response to injury or disease1. Many individuals with Marfan syndrome (MFS), caused by a deficiency of extracellular fibrillin-1, exhibit myopathy and of...
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Article
A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2
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 perturbatio...
