{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T21:58:36Z","timestamp":1783979916889,"version":"3.55.0"},"reference-count":57,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["5T32DK063688"],"award-info":[{"award-number":["5T32DK063688"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>NPR2 encodes atrial natriuretic peptide receptor B (ANPRB), a regulator of skeletal growth. Biallelic loss-of-function mutations in NPR2 result in acromesomelic dysplasia Maroteaux type (AMDM; OMIM 602875), while heterozygous mutations may account for 2% to 6% of idiopathic short stature (ISS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Describe the physical proportions and growth characteristics of an extended family with novel NPR2 mutations including members with AMDM, ISS, or normal stature.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Participants<\/jats:title>\n                  <jats:p>We performed whole exome sequencing in 2 healthy parents and 2 children with AMDM. Detailed genotyping and phenotyping were performed on members of a multigenerational family in an academic medical center. We expressed mutant proteins in mammalian cells and characterized expression and function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The sisters with AMDM were compound heterozygotes for missense mutations in the NPR2 gene, a novel p.P93S (maternal) and the previously reported p.R989L (paternal). Both mutant ANPRB proteins were normally expressed in HEK293T cells and exhibited dominant negative effects on wild-type ANPRB catalytic activity. Heterozygous relatives had proportionate short stature (height z-scores \u22122.06 \u00b1 0.97, median \u00b1 SD) compared with their wild-type siblings (\u22121.37 \u00b1 0.59). Height z-scores progressively and significantly decreased as NPR2-heterozygous children matured, while remaining constant in their wild-type siblings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Biallelic NPR2 mutations cause severe skeletal dysplasia (AMDM), whereas heterozygous mutations lead to a subtler phenotype characterized by progressive short stature with by increasing loss of height potential with age.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa491","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T14:37:14Z","timestamp":1595947034000},"page":"3190-3202","source":"Crossref","is-referenced-by-count":22,"title":["Short Stature is Progressive in Patients with Heterozygous <i>NPR2<\/i> Mutations"],"prefix":"10.1210","volume":"105","author":[{"given":"Patrick C","family":"Hanley","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Nemours Alfred I. duPont Hospital for Children, Wilmington, Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsh S","family":"Kanwar","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes and Center for Bone Health, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1550-2420","authenticated-orcid":false,"given":"Corine","family":"Martineau","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes and Center for Bone Health, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0036-7809","authenticated-orcid":false,"given":"Michael 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