{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:42:10Z","timestamp":1790480530257,"version":"4.1.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, \u2018sporadic\u2019 bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (\n                    <jats:italic>PDE2A<\/jats:italic>\n                    ) and 3B (\n                    <jats:italic>PDE3B<\/jats:italic>\n                    ) genes were identified in three patients. The\n                    <jats:italic>PDE2A<\/jats:italic>\n                    heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two\n                    <jats:italic>PDE3B<\/jats:italic>\n                    heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and\/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring\n                    <jats:italic>PDE2A<\/jats:italic>\n                    and\n                    <jats:italic>PDE3B<\/jats:italic>\n                    variants.\n                    <jats:italic>PDE2A<\/jats:italic>\n                    and\n                    <jats:italic>PDE3B<\/jats:italic>\n                    variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly,\n                    <jats:italic>PDE2A<\/jats:italic>\n                    and\n                    <jats:italic>PDE3B<\/jats:italic>\n                    variants increased SGK1 and SCNN1G\/ENaCg at mRNA or protein levels. In conclusion,\n                    <jats:italic>PDE2A<\/jats:italic>\n                    and\n                    <jats:italic>PDE3B<\/jats:italic>\n                    variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of genetic etiologies of PA.\n                  <\/jats:p>","DOI":"10.1530\/erc-20-0384","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T17:16:21Z","timestamp":1603127781000},"page":"1-13","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":22,"title":["Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism"],"prefix":"10.1530","volume":"28","author":[{"given":"Marcela","family":"Rassi-Cruz","sequence":"first","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea G","family":"Maria","sequence":"additional","affiliation":[{"name":"2Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio R","family":"Faucz","sequence":"additional","affiliation":[{"name":"2Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edra","family":"London","sequence":"additional","affiliation":[{"name":"2Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia A P","family":"Vilela","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas S","family":"Santana","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Flavia F","family":"Benedetti","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana S","family":"Goldbaum","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Y","family":"Tanno","sequence":"additional","affiliation":[{"name":"3Servi\u00e7o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor","family":"Srougi","sequence":"additional","affiliation":[{"name":"3Servi\u00e7o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L","family":"Chambo","sequence":"additional","affiliation":[{"name":"3Servi\u00e7o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Adelaide A","family":"Pereira","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline C B S","family":"Cavalcante","sequence":"additional","affiliation":[{"name":"4Instituto de Radiologia InRad, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco C","family":"Carnevale","sequence":"additional","affiliation":[{"name":"4Instituto de Radiologia InRad, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Pilan","sequence":"additional","affiliation":[{"name":"4Instituto de Radiologia InRad, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz A","family":"Bortolotto","sequence":"additional","affiliation":[{"name":"5Unidade de Hipertens\u00e3o, Instituto do Cora\u00e7\u00e3o (InCor), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"F Drager","sequence":"additional","affiliation":[{"name":"5Unidade de Hipertens\u00e3o, Instituto do Cora\u00e7\u00e3o (InCor), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"},{"name":"6Unidade de Hipertens\u00e3o, Disciplina de Nefrologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio M","family":"Lerario","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"},{"name":"7Endocrinology, Metabolism and Diabetes, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Candida B V","family":"Fragoso","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"},{"name":"8Servico de Endocrinologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo (ICESP), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice B","family":"Mendonca","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Claudia N","family":"Zerbini","sequence":"additional","affiliation":[{"name":"9Divis\u00e3o de Anatomia Patol\u00f3gica, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine A","family":"Stratakis","sequence":"additional","affiliation":[{"name":"2Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madson Q","family":"Almeida","sequence":"additional","affiliation":[{"name":"1Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"},{"name":"8Servico de Endocrinologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo (ICESP), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/28\/1\/ERC-20-0384.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/28\/1\/ERC-20-0384.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:51Z","timestamp":1784555751000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/28\/1\/1-13\/25478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/erc-20-0384","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]}}}