Nonsyndromic Peripheral Pulmonary Artery Stenosis Is Associated With Homozygosity of RNF213 p.Arg4810Lys Regardless of Co-occurrence of Moyamoya Disease

Chang, Sung-A; Song, Ju Sun; Park, Taek Kyu; Yang, Jeong Hoon; Kwon, Woo Chan; Kim, So Ree; Kim, Sung Mok; Cha, Jihoon; Jang, Shin Yi; Cho, Young Seok; Kim, Tae Jung; Bang, Oh Young; Song, June O.; Ki, Chang‐Seok; Kim, Duk Kyung

doi:10.1016/j.chest.2017.09.023

Cited by 54 publications

(46 citation statements)

References 26 publications

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“…11,12 Intriguingly, the penetrance of this specific founder mutation must be low, but if disease phenotypes based on this mutation appear, vascular diseases in several organs, at least in the brain and lung, are induced. 5,6 We previously reported one family with the RNF213 p.Arg4810Lys variant in which the mother developed PAH (Case #4), and her daughter exhibited Moyamoya disease, 3 suggesting the presence of RNF213-associated vascular diseases. A previous in vitro study demonstrated that angiogenic activities in induced pluripotent stem cells from patients with Moyamoya disease and RNF213 R4859K are reduced.…”

Section: Discussionmentioning

confidence: 99%

“…3 This RNF213 p.Arg4810Lys allele is well known to have a susceptive relationship with Moyamoya disease, a cerebral vascular disease, 4 and recent human studies, including our own, indicate that the RNF213 p.Arg4810Lys variant also confers a risk for extracranial vascular diseases, including peripheral pulmonary stenosis. 5,6 Previous in vitro studies demonstrated that this specific variant modifies the protein's function and lowers the angiogenic activity in endothelial cells. 7,8 These findings suggest that PAH can be added as a new member of RNF213-associated vascular diseases.…”

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confidence: 99%

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Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension

Hiraide

Kataoka

Suzuki

et al. 2020

The Journal of Heart and Lung Transplantation

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BACKGROUND: A variant of c.14429G>A (p.Arg4810Lys, rs112735431) in the ring finger protein 213 gene (RNF213; NM_001256071.2) has been recently identified as a risk allele for pulmonary arterial hypertension (PAH). PAH can be added as a new member of RNF213-associated vascular diseases, which include Moyamoya disease and peripheral pulmonary stenosis. Our aim was to identify the clinical features and outcomes of PAH patients with this variant. METHODS: Whole-exome sequencing was performed in 139 idiopathic (or possibly heritable) PAH patients. RESULTS: The RNF213 p.Arg4810Lys variant was identified in a heterozygous state in 11 patients (7.9%). Time-course changes in hemodynamics after combination therapy in the patients with the RNF213 p.Arg4810Lys variant were significantly poorer compared with those carrying the bone morphogenic protein receptor type 2 (BMPR2) mutation (n = 36) (comparison of changes in mean pulmonary arterial pressure, p = 0.007). The event-free rate of death or lung transplantation was significantly poorer in RNF213 p.Arg4810Lys variant carriers than in BMPR2 mutation carriers (5-year event-free rate since the introduction of prostaglandin I 2 infusion, 0% vs 93%, respectively; p < 0.001).

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension

Hiraide

Kataoka

Suzuki

et al. 2020

The Journal of Heart and Lung Transplantation

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“…Our patient's coronary angiography showed several areas where the vessel resembles a string of beads, which is best seen in the distal OM branch and distal RCA (Figures 3, 4, and 5). The string of bead appearance has been previously described in other vessels such as the peripheral pulmonary, renal, and carotid arteries as a direct result of intimal thickening [6]. This distinct pattern helps clinicians distinguish CAD in Moyamoya disease from CAD in the setting of atherosclerosis using coronary angiography.…”

Section: Discussionmentioning

confidence: 75%

“…The p.Arg4810Lys variant, commonly found in the Eastern Asian population, is thought to cause the classic intracranial vasculopathy when in the heterozygous state. However, individuals that possess the homozygous variant seem to develop systemic vasculopathy and more severe symptoms [6]. The link between the RNF variant, p.Arg4810Lys, and Moyamoya disease has potential to be a screening tool for the risk of systemic disease and disease severity.…”

Section: Discussionmentioning

confidence: 99%

ST-Elevation Myocardial Infarction (STEMI) in a Patient with Moyamoya Disease

Livesay

Johnson

2019

Case Reports in Cardiology

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Moyamoya disease is a rare condition that is primarily reported in Asian populations, characterized by stenoocclusive intracranial angiopathy with small, fragile, and multiple collateral vessel formation. Extracranial complications, mainly abnormalities within the renal vasculature, have been described; however, there are very few case reports of cardiovascular complications in patients with Moyamoya disease. We report a 26-year-old Caucasian female with known Moyamoya disease who presented with both typical and atypical chest pain, mimicking symptoms of a previous non-ST-elevation myocardial infarction. Approximately six months prior to the current hospital admission, she underwent coronary angiography requiring percutaneous coronary intervention (PCI) with two drug-eluting stents to the right coronary artery (RCA) for a critical stenosis. Despite medical management, our patient developed inferior lead ST-elevations leading to a repeat left heart catheterization which showed clinically significant stenosis of the first obtuse marginal branch. Development of significant coronary artery stenosis in a short period of time demonstrates the clinical significance of minimal atherosclerosis in the setting of underlying fibrocellular thickening as seen in patients with Moyamoya disease. Clinicians need to be aware of the possibility of coronary involvement in addition to intracranial vascular complications in patients with Moyamoya disease and take appropriate measures to prevent or delay the development of atherosclerosis in these arteries.

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“…7 The phenotypic heterogeneity described among patients with an RNF213 p.Arg4810Lys mutation is also notable, as different vascular circuits may be affected, and abnormalities are reported across different caliber vessels within the pulmonary vasculature. 8 This, in and of itself, is not unique; the BMPR2 germline mutations have been reported in patients with PAH as well as pulmonary venoocclusive disease, 9 which are distinct vascular entities. Yet, divergence in the clinical phenotype associated with the same genetic variant reinforces the need for greater study on environmental cues or other acquired factors that interact with the genetic basis of disease.…”

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confidence: 99%

Pulmonary arterial hypertension in the modern era: The intersection of genotype and phenotype

Ruopp

Maron

2020

The Journal of Heart and Lung Transplantation

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Nonsyndromic Peripheral Pulmonary Artery Stenosis Is Associated With Homozygosity of RNF213 p.Arg4810Lys Regardless of Co-occurrence of Moyamoya Disease

Cited by 54 publications

References 26 publications

Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension

Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension

ST-Elevation Myocardial Infarction (STEMI) in a Patient with Moyamoya Disease

Pulmonary arterial hypertension in the modern era: The intersection of genotype and phenotype

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