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

TY - JOUR

T1 - Exome data clouds the pathogenicity of genetic variants in Pulmonary Arterial Hypertension

AU - Abbasi, Yeganeh

AU - Jabbari, Javad

AU - Jabbari, Reza

AU - Glinge, Charlotte

AU - Izadyar, Seyed Bahador

AU - Spiekerkoetter, Edda

AU - Zamanian, Roham T.

AU - Carlsen, Jørn

AU - Tfelt-Hansen, Jacob

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

KW - ESP

KW - exome sequencing project

KW - HGMD

KW - PAH-associated gene

KW - pulmonary arterial hypertension

UR - http://www.scopus.com/inward/record.url?scp=85052646997&partnerID=8YFLogxK

U2 - 10.1002/mgg3.452

DO - 10.1002/mgg3.452

M3 - Journal article

C2 - 30084161

AN - SCOPUS:85052646997

SN - 2324-9269

VL - 6

SP - 835

EP - 844

JO - Molecular Genetics and Genomic Medicine

JF - Molecular Genetics and Genomic Medicine

IS - 5

ER -