Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Sep;6(5):835-844.
doi: 10.1002/mgg3.452. Epub 2018 Aug 6.

Exome data clouds the pathogenicity of genetic variants in Pulmonary Arterial Hypertension

Affiliations
Review

Exome data clouds the pathogenicity of genetic variants in Pulmonary Arterial Hypertension

Yeganeh Abbasi et al. Mol Genet Genomic Med. 2018 Sep.

Abstract

Background: We aimed to provide a set of previously reported PAH-associated missense and nonsense variants, and evaluate the pathogenicity of those variants.

Methods: The Human Gene Mutation Database, PubMed, and Google Scholar were searched for previously reported PAH-associated genes and variants. Thereafter, both exome sequencing project and exome aggregation consortium as background population searched for previously reported PAH-associated missense and nonsense variants. The pathogenicity of previously reported PAH-associated missense variants evaluated by using four in silico prediction tools.

Results: In total, 14 PAH-associated genes and 180 missense and nonsense variants were gathered. The BMPR2, the most frequent reported gene, encompasses 135 of 180 missense and nonsense variants. The exome sequencing project comprised 9, and the exome aggregation consortium counted 25 of 180 PAH-associated missense and nonsense variants. The TOPBP1 and ENG genes are unlikely to be the monogenic cause of PAH pathogenesis based on allele frequency in background population and prediction analysis.

Conclusion: This is the first evaluation of previously reported PAH-associated missense and nonsense variants. The BMPR2 identified as the major gene out of 14 PAH-associated genes. Based on findings, the ENG and TOPBP1 gene are not likely to be the monogenic cause of PAH.

Keywords: ESP; HGMD; PAH-associated gene; exome sequencing project; pulmonary arterial hypertension.

PubMed Disclaimer

References

    1. Abbasi, Y. , Jabbari, J. , Jabbari, R. , Yang, R. Q. , Risgaard, B. , Køber, L. , … Tfelt‐Hansen, J. (2016). The pathogenicity of genetic variants previously associated with left ventricular non‐compaction. Molecular Genetics and Genomic Medicine, 4(2), 135–142. 10.1002/mgg3.182 - DOI - PMC - PubMed
    1. Austin, E. D. , & Loyd, J. E. (2014). The genetics of pulmonary arterial hypertension. Circulation Research, 115(1), 189–202. 10.1161/CIRCRESAHA.115.303404 - DOI - PMC - PubMed
    1. Austin, E. D. , Loyd, J. E. , & Phillips, J. A . (1993). Heritable pulmonary arterial hypertension In Adam M. P., Ardinger H. H. & Pagon R. A., et al. (Eds.) GeneReviews®. Seattle, WA: University of Washington, Seattle. http://www.ncbi.nlm.nih.gov/books/NBK1485/. Accessed April 16, 2018.
    1. Austin, E. D. , Ma, L. , LeDuc, C. , Berman Rosenzweig, E. , Borczuk, A. , Phillips, J. A. 3rd, … Chung, W. K. (2012). Whole exome sequencing to identify a novel gene (caveolin‐1) associated with human pulmonary arterial hypertension. Circulation: Cardiovascular Genetics, 5(3), 336–343. 10.1161/CIRCGENETICS.111.961888 - DOI - PMC - PubMed
    1. Badesch, D. B. , Champion, H. C. , Sanchez, M. A. G. , Hoeper, M. M. , Loyd, J. E. , Manes, A. , … Torbicki, A. (2009). Diagnosis and assessment of pulmonary arterial hypertension. Journal of the American College of Cardiology, 54(1 Suppl), S55–S66. 10.1016/j.jacc.2009.04.011 - DOI - PubMed

Publication types

Grants and funding

LinkOut - more resources