{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:33:27Z","timestamp":1787016807336,"version":"build-2736575974"},"reference-count":22,"publisher":"BMJ","issue":"5","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2019,5,5]]},"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>CACNA1H<\/jats:italic>\n                    gene encodes the pore-forming \u03b11 subunit of the T-type voltage-dependent calcium channel Ca\n                    <jats:sub>V<\/jats:sub>\n                    3.2, expressed abundantly in the adrenal cortex. Mutations in\n                    <jats:italic>CACNA1H<\/jats:italic>\n                    are associated with various forms of primary aldosteronism (PA), including familial hyperaldosteronism type 4 (FH4). We describe a patient with refractory hypokalaemia and elevated aldosterone secretion independent of renin activity. Despite the absence of overt hypertension in this patient, the laboratory evaluation was consistent with a diagnosis of PA. Whole-exome sequencing revealed a de novo missense variant, R890H, in the voltage sensing domain of\n                    <jats:italic>CACNA1H<\/jats:italic>\n                    . Expression of the variant channel in cells resulted in decreased whole-cell current, consistent with a loss-of-function. We hypothesise this variant is the genetic cause of pathological aldosterone secretion in this patient, and thereby expand the current understanding of the genetic basis of FH4.\n                  <\/jats:p>","DOI":"10.1136\/bcr-2018-229031","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T06:04:09Z","timestamp":1558677849000},"page":"e229031","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Primary aldosteronism associated with a germline variant in\n                    <i>CACNA1H<\/i>"],"prefix":"10.1136","volume":"12","author":[{"given":"Kendra","family":"Wulczyn","sequence":"first","affiliation":[{"name":"Department of Medicine, UCSF, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Perez-Reyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L","family":"Nussbaum","sequence":"additional","affiliation":[{"name":"Invitae Corporation, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medicine, UCSF, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,5,23]]},"reference":[{"key":"2025082723535455000_12.5.e229031.1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000079505.25750.11"},{"key":"2025082723535455000_12.5.e229031.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.01.052"},{"key":"2025082723535455000_12.5.e229031.3","first-page":"204","article-title":"[Hypertension caused by tumors of the adrenal cortex]","volume":"8","author":"Litynski","year":"1953","journal-title":"Pol Tyg Lek"},{"key":"2025082723535455000_12.5.e229031.4","first-page":"257","article-title":"The evolution of primary aldosteronism: 1954-1967","volume":"62","author":"Conn","year":"1966","journal-title":"Harvey Lect"},{"key":"2025082723535455000_12.5.e229031.5","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(83)91022-7"},{"key":"2025082723535455000_12.5.e229031.6","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1210\/er.2018-00139","article-title":"The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment","volume":"39","author":"Vaidya","year":"2018","journal-title":"Endocr Rev"},{"key":"2025082723535455000_12.5.e229031.7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031337"},{"key":"2025082723535455000_12.5.e229031.8","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1161\/HYPERTENSIONAHA.116.08952","article-title":"Continuum of Renin-Independent Aldosteronism in Normotension","volume":"69","author":"Baudrand","year":"2017","journal-title":"Hypertension"},{"key":"2025082723535455000_12.5.e229031.9","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3353"},{"key":"2025082723535455000_12.5.e229031.10","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0151"},{"key":"2025082723535455000_12.5.e229031.11","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1161\/HYPERTENSIONAHA.117.10111","article-title":"Old and New Concepts in the Molecular Pathogenesis of Primary Aldosteronism","volume":"70","author":"Prada","year":"2017","journal-title":"Hypertension"},{"key":"2025082723535455000_12.5.e229031.12","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1210\/er.2017-00189","article-title":"Genetic Causes of Functional Adrenocortical Adenomas","volume":"38","author":"Zennaro","year":"2017","journal-title":"Endocr Rev"},{"key":"2025082723535455000_12.5.e229031.13","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1161\/HYPERTENSIONAHA.118.11150","article-title":"Saga of Familial Hyperaldosteronism: Yet a New Channel","volume":"71","author":"Lenzini","year":"2018","journal-title":"Hypertension"},{"key":"2025082723535455000_12.5.e229031.14","unstructured":"Karczewski KJ , Francioli LC , Tiao G , et al . Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of- function intolerance across human protein-coding genes."},{"key":"2025082723535455000_12.5.e229031.15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.104190"},{"key":"2025082723535455000_12.5.e229031.16","unstructured":"Gilbert S , Weiner D , Bomback A , et al . Nation Kidney Foundation\u2019s Primer On Kidney Diseases. Philadelphia, PA: Elsevier, Inc, 2018:97\u2013106."},{"key":"2025082723535455000_12.5.e229031.17","unstructured":"Kronenberg H , Melmed S , Polonsky K , et al . Williams Textbook of Endocrinology. 11th\u00a0ed. 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