TNFRSF13B c.226G>A (p.Gly76Ser) as a Novel Causative Mutation for Pulmonary Arterial Hypertension

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

卷:10

Kenjiro Kosaki¹  Hisato Suzuki¹  Mizuki Momoi²  Takahiro Hiraide²  Motoaki Sano²  Yoshinori Katsumata²  Masaharu Kataoka²  Keiichi Fukuda²  Jin Endo²  Shinichi Goto²  Yoshiki Shinya²  Yutaka Kurebayashi³ 

[1] Center for Medical Genetics Keio University School of Medicine Tokyo Japan;

[2] Department of Cardiology Keio University School of Medicine Tokyo Japan;

[3] Institute for Integrated Sports Medicine Keio University School of Medicine Tokyo Japan;

关键词: genetics;    pulmonary arterial hypertension;    structural analysis;    TNFRSF13B;    whole‐exome sequencing;   

DOI  :  10.1161/JAHA.120.019245

来源: DOAJ

【 摘 要 】

Background Recently, some studies reported the pulmonary artery hypertension (PAH)–associated genes. However, a majority of patients with familial or sporadic PAH lack variants in the known pathogenic genes. In this study, we investigated the new causative gene variants associated with PAH. Methods and Results Whole‐exome sequencing in 242 Japanese patients with familial or sporadic PAH identified a heterozygous substitution change involving c.226G>A (p.Gly76Ser) in tumor necrotic factor receptor superfamily 13B gene (TNFRSF13B) in 6 (2.5%) patients. TNFRSF13B controls the differentiation of B cell and secretion of inflammatory cytokines and may be involved in vascular inflammation. In silico structural analysis simulation demonstrated the structural instability of the N‐terminal region of the protein synthesized from TNFRSF13B p.Gly76Ser variant. These suggest that the TNFRSF13B p.Gly76Ser variant may be involved in the development of PAH via aberrant inflammation in pulmonary vessels. Conclusions TNFRSF13B p.Gly76Ser variant is a candidate of novel causative gene variant for PAH.

【 授权许可】

Unknown