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
VL - 6
SP - 835
EP - 844
JO - Molecular genetics & genomic medicine
JF - Molecular genetics & genomic medicine
SN - 2324-9269
IS - 5
ER -