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We studied two pediatric patients homozygous for <jats:italic>GDF2<\/jats:italic> (BMP9 gene) nonsense mutations: one with PAH (c.[76C&gt;T];[76C&gt;T] or p.[Gln26Ter];[Gln26Ter] and a new individual with pulmonary arteriovenous malformations (PAVMs; c.[835G&gt;T];[835G&gt;T] or p.[Glu279Ter];[Glu279Ter]); both with facial telangiectases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma samples were assayed for BMP9 and BMP10 by ELISA. In parallel, serum BMP activity was assayed using an endothelial BRE\u2010luciferase reporter cell line (HMEC1\u2010BRE). Proteins were expressed for assessment of secretion and processing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma levels of both BMP9 and BMP10 were undetectable in the two homozygous index cases and this corresponded to low serum\u2010derived endothelial BMP activity in the patients. Measured BMP9 and BMP10 levels were reduced in the asymptomatic heterozygous p.[Glu279Ter] parents, but serum activity was normal. Although expression studies suggested alternate translation can be initiated at Met57 in the p.[Gln26Ter] mutant, this does not result in secretion of functional BMP9.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, these data show that homozygous <jats:italic>GDF2<\/jats:italic> mutations, leading to a loss of circulating BMP9 and BMP10, can cause either pediatric PAH and\/or \u201cHHT\u2010like\u201d telangiectases and PAVMs. Although patients reported to date have manifestations that overlap with those of HHT, none meet the Cura\u00e7ao criteria for HHT and seem distinct from HHT in terms of the location and appearance of telangiectases, and a tendency for tiny, diffuse PAVMs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1685","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T07:09:24Z","timestamp":1617952164000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Homozygous <i>GDF2<\/i> nonsense mutations result in a loss of circulating BMP9 and BMP10 and are associated with either PAH or an \u201cHHT\u2010like\u201d syndrome in children"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8423-0935","authenticated-orcid":false,"given":"Joshua","family":"Hodgson","sequence":"first","affiliation":[{"name":"Department of Medicine University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1430-9618","authenticated-orcid":false,"given":"Lidia","family":"Ruiz\u2010Llorente","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas Margarita Salas Consejo Superior de Investigaciones Cient\u00edficas (CSIC), and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Madrid Spain"},{"name":"Department of Systems Biology School of Medicine and Health Sciences University of Alcal\u00e1 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9939-7922","authenticated-orcid":false,"given":"Jamie","family":"McDonald","sequence":"additional","affiliation":[{"name":"HHT Center Department of Pathology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-9051","authenticated-orcid":false,"given":"Oliver","family":"Quarrell","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Sheffield Children\u2019s Hospital Sheffield 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