Association between RNF213 c.14576G>A Variant (rs112735431) and Peripheral Pulmonary Artery Stenosis in Moyamoya Disease

Background: Moyamoya disease (MMD) and peripheral pulmonary artery stenosis (PPAS) are relatively rare and demonstrate steno-occlusive vascular lesions in different organs. Genetic studies identified RNF213 polymorphism c.14576G>A (rs112735431) as a susceptibility variant for East Asian MMD. RNF213 polymorphism c.14576G>A is further associated with various vascular lesions of other organs. In this study, we aimed to clarify the incidence and clinical manifestations of PPAS in MMD patients and analyze the correlation between RNF213 genotype and PPAS. Methods: This retrospective case-control study investigated the association between RNF213 polymorphism and PPAS in 306 MMD/quasi-MMD patients, reviewing the medical charts and imaging records of consecutive patients with MMD admitted from January 2015 to December 2020. Results: PPAS was observed in 3 MMD/quasi-MMD patients (0.98%, 3/306). RNF213 polymorphism c.14576G>A was determined for all 306 MMD/quasi-MMD patients. The incidence of PPAS in RNF213-wildtype, RNF213-heterozygote, and RNF213-homozygote MMD/quasi-MMD patients was 0% (0/101), 0.5% (1/200), and 40% (2/5), respectively. The association between PPAS and homozygote polymorphism of RNF213 c.14576G>A was statistically significant in MMD/quasi-MMD patients (p = 0.0018). In all cases, pulmonary artery hypertension due to PPAS was evident during their childhood and young adolescent stages. Surgical indications for MMD were discouraged in 1 case due to her severe cardiopulmonary dysfunction. Conclusions: The homozygote variant of RNF213 polymorphism c.14576G>A can be a potential predisposing factor for PPAS in MMD/quasi-MMD patients. Despite the relatively rare entity, PPAS should be noted to determine surgical indications for MMD/quasi-MMD patients.

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

CHEST Journal ◽

10.1016/j.chest.2017.09.023 ◽

2018 ◽

Vol 153 (2) ◽

pp. 404-413 ◽

Cited By ~ 17

Author(s):

Sung-A Chang ◽

Ju Sun Song ◽

Taek Kyu Park ◽

Jeong Hoon Yang ◽

Woo Chan Kwon ◽

...

Keyword(s):

Pulmonary Artery ◽

Moyamoya Disease ◽

Artery Stenosis ◽

Pulmonary Artery Stenosis

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A histopathological report of a 16-year-old male with peripheral pulmonary artery stenosis and Moyamoya disease with a homozygous RNF213 mutation

Respiratory Medicine Case Reports ◽

10.1016/j.rmcr.2019.100977 ◽

2020 ◽

Vol 29 ◽

pp. 100977

Author(s):

Kei Takahashi ◽

Junichi Nakamura ◽

Shinya Sakiyama ◽

Toshitaka Nakaya ◽

Takahiro Sato ◽

...

Keyword(s):

Pulmonary Artery ◽

Moyamoya Disease ◽

Artery Stenosis ◽

Pulmonary Artery Stenosis ◽

Histopathological Report

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Pulmonary artery stenosis murmurs. A new diagnostic sign of pulmonary embolism

Archives of Internal Medicine ◽

10.1001/archinte.121.1.97 ◽

1968 ◽

Vol 121 (1) ◽

pp. 97-100

Author(s):

B. S. Chertow

Keyword(s):

Pulmonary Embolism ◽

Pulmonary Artery ◽

Artery Stenosis ◽

Pulmonary Artery Stenosis ◽

Diagnostic Sign

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Increased Airway Pressure and Simulated Branch Pulmonary Artery Stenosis Increase Pulmonary Regurgitation After Repair of Tetralogy of Fallot

Circulation ◽

10.1161/01.cir.95.3.643 ◽

1997 ◽

Vol 95 (3) ◽

pp. 643-649 ◽

Cited By ~ 76

Author(s):

Rajiv R. Chaturvedi ◽

Philip J. Kilner ◽

Paul A. White ◽

Andrew Bishop ◽

Richard Szwarc ◽

...

Keyword(s):

Pulmonary Artery ◽

Tetralogy Of Fallot ◽

Airway Pressure ◽

Pulmonary Regurgitation ◽

Artery Stenosis ◽

Pulmonary Artery Stenosis ◽

Branch Pulmonary Artery ◽

Branch Pulmonary Artery Stenosis

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Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis

Scientific Reports ◽

10.1038/s41598-021-93736-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cuilan Hou ◽

Junmin Zheng ◽

Wei liu ◽

Lijian Xie ◽

Xiaomin Sun ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Pulmonary Artery ◽

Molecular Mechanism ◽

Protein Level ◽

Congenital Heart ◽

Artery Stenosis ◽

Pulmonary Artery Stenosis ◽

Functional Component ◽

Functional Changes

AbstractCongenital heart defects, one of the most common birth defects, affect approximately 1% of live birth globally and remain the leading cause of infant mortality in developed countries. Utilizing the pathogenicity score and inheritance mode from whole exome sequencing results, a heterozygous mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) in elastin (ELN) was identified among 6,440 variants in a female proband born with an atrial septal defect accompanied by pulmonary artery stenosis. Results of RT-PCR showed that the mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) did not affect the expression levels of ELN mRNA but increased protein level. The content of ELN truncate (functional component) was significantly lower in both the intracellular and extracellular compartments after mutation. These results indicate that the ELN mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) affected the protein truncate, which may be a functional component of ELN and play crucial roles for this pedigree. Here we report of an ELN heterozygous variant associated with congenital heart disease accompanied with pulmonary artery stenosis, which is less common. Based on our results, we speculate that this may be the main molecular mechanism underlying the mutation-led functional changes, and propose that the decrease of ELN protein level may cause this pedigree vascular abnormality, especially pulmonary artery stenosis, and reinforce the view that ELN insufficiency is the primary cause of these vascular lesions. This may be the main molecular mechanism underlying the mutation-led functional changes. Thus, systematic analysis not only enables us to better understand the etiology of this disease but also contributes to clinical and prenatal diagnosis.

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