Features of Vascular Ehlers-Danlos Syndrome Among Biobank Participants Harboring Predicted High-Risk
            <i>COL3A1</i>
            Genotypes

Lui, Madeline M; Shadrina, Mariya; Gelb, Bruce D.; Kontorovich, Amy

doi:10.1161/circgen.122.003864

Cited by 5 publications

(2 citation statements)

References 5 publications

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“…Vascular Ehlers-Danlos syndrome (vEDS), also known as EDS type IV, is characterized by translucent skin, joint hypermobility, and a high risk of arterial rupture. [ 1 ] The incidence of vEDS is approximately one in 150,000. [ 2 ] COL3A1 gene heterozygous mutations can cause vEDS, which encodes the pro-α1 (III) chain of type III procollagen.…”

Section: Introductionmentioning

confidence: 99%

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Case report of a young male, with recurrent pneumothorax, hemoptysis and intrapulmonary cavitary lesions

Junping,

Tianyu,

Rentao

et al. 2023

Medicine

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Rationale: Primary spontaneous pneumothorax (PSP) is a manifestation of Vascular Ehlers-Danlos syndrome (vEDS) caused by heterozygous mutations in the COL3A1 gene. vEDS is a rare inherited disorder with an prevalence of one in 150,000. It can causes PSP and severe fragility of connective tissues with arterial but it remains poorly defined on clinical grounds and diagnose. Through this report, we hoped to help clinicians further understand the characteristics of vEDS. Patient concerns: A 22-year-old man presented with recurrent pneumothorax, hemoptysis, and chest pain. Physical examination revealed remarkable hypermobility of the small joints and translucent skin with visible veins. Chest computed tomography (CT) showed pneumothorax and multiple pulmonary cavities. Intervention and outcome: Genomic deoxyribonucleic acid (DNA) was extracted from patients. Heterozygosity was observed in all 3 novel variants. The main variant is COL3A1, c.3256-43T > G(NM_000090.3), which represents a missense mutation in collagen type III alpha 1 that can lead to vEDS. The other 2 mutations were FLNB c.4814G > A(NM_001457.3) and TSC2 c.3145G > A (NM_000548.3). These variants were validated by Sanger sequencing of their parents. COL3A1was not detected in either of the parent strains. FLNB and TSC2 were detected in his mother. Diagnoses: Vascular Ehlers-Danlos syndrome. Lessons: Both COL3A1 and TSC2 gene mutations can cause PSP; however, to the best of our knowledge, there are no reports on these 2 gene mutations in 1 patient at the same time.

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Section: Introductionmentioning

confidence: 99%

“…Ninety patients with vEDS present with external thoracic arterial dissection or rupture. [ 1 ] vEDS is generally considered the most severe form of EDS.…”

Section: Introductionmentioning

confidence: 99%

Case report of a young male, with recurrent pneumothorax, hemoptysis and intrapulmonary cavitary lesions

Junping,

Tianyu,

Rentao

et al. 2023

Medicine

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Ready or not, genomic screening of fetuses is already here

Gold,

Nadel,

Green

2024

Genetics in Medicine

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The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-β signalling

He,

IJpma,

Vreeken

et al. 2024

Cardiovascular Research

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Aim Aortic aneurysms (AA) frequently involve dysregulation of transforming growth factor β (TGF-β)-signaling in the aorta. Here, FURIN was tested as aneurysm predisposition gene given its role as proprotein convertase in pro-TGF-β maturation. Methods and results Rare FURIN variants were detected by whole-exome sequencing of 781 unrelated aortic aneurysm patients and affected relatives. Thirteen rare heterozygous FURIN variants occurred in 3.7% (29) unrelated index AA patients, of which 72% had multiple aneurysms or a dissection. FURIN maturation and activity of these variants were decreased in vitro. Patient-derived fibroblasts showed decreased pro-TGF-β processing, phosphorylation of downstream effector SMAD2 and kinases ERK1/2, and steady-state mRNA levels of the TGF-β-responsive ACTA2 gene. In aortic tissue, collagen and fibrillin fibers were affected. One variant (R745Q), observed in 10 unrelated cases, affected TGF-β signaling variably, indicating effect modification by individual genetic backgrounds. Conclusion FURIN is a novel, frequent genetic predisposition for abdominal-, thoracic-, and multiple aortic or middle sized artery aneurysms in older patients, by affecting intracellular TGF-β signaling, depending on individual genetic backgrounds.

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Features of Vascular Ehlers-Danlos Syndrome Among Biobank Participants Harboring Predicted High-Risk COL3A1 Genotypes

Cited by 5 publications

References 5 publications

Case report of a young male, with recurrent pneumothorax, hemoptysis and intrapulmonary cavitary lesions

Case report of a young male, with recurrent pneumothorax, hemoptysis and intrapulmonary cavitary lesions

Ready or not, genomic screening of fetuses is already here

The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-β signalling

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