2017 Fiscal Year Final Research Report
Role of X Gene Variant in Childhood Pulmonary Arterial Hypertension
| Project/Area Number |
15K19639
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Nagai Ayako 東京女子医科大学, 医学部, 研究生 (10622160)
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| Research Collaborator |
NAKANISHI Toshio
FURUTANI Yoshiyuki
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 肺動脈性肺高血圧症 / 遺伝子変異 |
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| Outline of Final Research Achievements |
In order to find novel disease-causing variants in patients with pulmonary arterial hypertension, we performed direct sequencing and multiplex ligation-dependent probe amplification to analyze 18 families with multiple affected family members with PAH. In one of the 18 families with PAH, there were no disease-causing variants already-known. Whole-exome next-generation sequencing was performed in the family, and we identified a novel variant in X gene in the family. The variant, R554L-X, revealed gain-of-function and induced decreasing nucleus p53 and p21, lower phosphorylation of nucleus p53, decreasing apoptotic hPASMCs, and increasing hPASMCs proliferation and cell viability compared to wild-type X. This study can contribute to elucidate mechanism of PAH pathogenesis.
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| Free Research Field |
小児循環器分野
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