{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:18:20Z","timestamp":1790817500534,"version":"4.1.0"},"reference-count":28,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"CAMS Innovation Fund for Medical Science","award":["CAMS-2016-I2M-1-002"],"award-info":[{"award-number":["CAMS-2016-I2M-1-002"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC091500"],"award-info":[{"award-number":["2016YFC091500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The natriuretic peptide receptor 2 gene (NPR2) is a causative gene of idiopathic short stature (ISS) with an incidence rate of 2% to 6%. The clinical characteristics of patients with NPR2 heterozygous mutations are atypical, and data on the efficacy of recombinant human growth hormone (rhGH) treatment in patients with NPR2 mutations are limited.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This work reports 6 cases with NPR2 mutation and explores the characteristics of patients with an NPR2 mutation and their therapeutic response to rhGH.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design, Settings, and Patients<\/jats:title>\n                  <jats:p>Six Chinese short-stature patients in our hospital with NPR2 mutations by whole-exome sequencing were included. We also searched all previously published NPR2 mutation cases as of August 10, 2020, and information about their medical history, mutations, and rhGH treatment were recorded and summarized.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The clinical characteristics of patients with an NPR2 heterozygous mutation mainly included short stature, facial anomalies, and skeletal dysplasia. Skeletal dysplasia mainly included brachydactyly (56.2%), shortened metacarpals or metatarsals (particularly fourth to fifth; 26.1%), and clinodactyly (21.7%). rhGH treatment significantly improved the height SD score (SDS) of patients with NPR2 heterozygous mutations (median, \u20132.1 vs \u20132.9, P &amp;lt; .001), especially in girls. The height SDS change correlated negatively with initial age of treatment (r = \u20130.477; P = .034), and height SDS change of patients with NPR2 heterozygous mutations in the carboxyl-terminal guanylyl cyclase catalytic domain was significantly higher than that of the extracellular ligand-binding region domain (median, 1.9 vs 0.6, P = .019).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ISS patients with skeletal deformities should be tested for an NPR2 mutation. rhGH treatment is beneficial for short-stature patients with NPR2 heterozygous mutations and needs further study.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa842","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T06:00:14Z","timestamp":1605679214000},"page":"431-441","source":"Crossref","is-referenced-by-count":26,"title":["Clinical Characteristics of Short-Stature Patients With an <i>NPR2<\/i> Mutation and the Therapeutic Response to rhGH"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4182-2890","authenticated-orcid":false,"given":"Xiaoan","family":"Ke","sequence":"first","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanting","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Miao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengying","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"issue":"11","key":"2021122205484225600_CIT0001","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.1210\/jc.2008-0509","article-title":"Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the 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