{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T01:27:35Z","timestamp":1767922055941,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102015\u2010054988"],"award-info":[{"award-number":["NRF\u20102015\u2010054988"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>C\u2010type natriuretic peptide (CNP, <jats:italic>NPPC<\/jats:italic>) and its receptor, natriuretic peptide receptor\u2010B (NPR\u2010B, <jats:italic>NPR2<\/jats:italic>), are critical for endochondral ossification. A monoallelic NPR2 mutation has been suggested to mildly impair long bone growth. This study was performed to identify the <jats:italic>NPR2<\/jats:italic> mutations in Korean patients with idiopathic short stature (ISS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>One hundred and sixteen subjects with nonsyndromic ISS were enrolled in this study, and the <jats:italic>NPPC<\/jats:italic> and <jats:italic>NPR2<\/jats:italic> were sequenced. In silico prediction and in vitro functional analysis, using a cell\u2010based assay, were performed to confirm their protein derangement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean age at diagnosis of ISS was 8.0\u00a0years, and the height <jats:italic>z<\/jats:italic>\u2010score was \u22122.65. Three pathogenic variants (R921Q, R495C, and Y598N) and one benign variant (R787W) of the <jats:italic>NPR2<\/jats:italic> were identified, while no novel sequence variant of the <jats:italic>NPPC<\/jats:italic> was found in all subjects. Two novel pathogenic mutants (R495C and Y598N) were predicted as highly pathogenic by several computational methods. In vitro study involving stimulation with CNP, R495C\u2010, and Y598N\u2010transfected cells showed decreased cGMP production compared to wild type\u2010transfected cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Heterozygous <jats:italic>NPR2<\/jats:italic> mutations were found in 2.6% of ISS Korean subjects. This prevalence and the dominant\u2010negative effect of mutant NPR\u2010B on growth signals imply that it is one of genetic causes of ISS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1146","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T07:10:01Z","timestamp":1579590601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Role of <i>NPR2<\/i> mutation in idiopathic short stature: Identification of two novel mutations"],"prefix":"10.1002","volume":"8","author":[{"given":"Il Tae","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Pediatrics Hallym University College of Medicine Chuncheoun Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine Tokyo 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