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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
A Novel Missense Variant of ZC3H12A in Pulmonary Arterial Hypertension
Ryotaro Asano1,2, Makoto Okazawa1, Tomohiko Ishibashi1
1Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute Osaka Japan.
Background:
Because Regnase-1, encoded by ZC3H12A, suppresses the development of pulmonary arterial hypertension (PAH) by controlling pro-inflammatory cytokines, we aimed to identify ZC3H12A variants in patients with PAH.
Methods And Results:
We analyzed whole-genome sequence data of patients with PAH to search for disease-associated ZC3H12A variants. The Regnase-1 p.D426G variant was identified in 2 patients, 1 of whom presented with prominent infiltration of inflammatory cells in the lung. The protein level of the variant was decreased in vitro.
Conclusions:
We identified a novel missense variant of ZC3H12A that is directly involved in regulating inflammation in patients with PAH.
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