FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4315702932> ?p ?o ?g. }

• W4315702932 endingPage "e38" @default.
• W4315702932 startingPage "e38" @default.
• W4315702932 abstract "The first reported (Sutherland et al. 1966) form of familial primary aldosteronism (PA) involved a father and son and was glucocorticoid-remediable (familial hyperaldosteronism type I, FH-I). In 1992, Lifton and colleagues elucidated its causation, a hybrid gene mutation composed of CYP11B1 (encoding 11beta-hydroxylase) regulatory sequences and CYP11B2 (aldosterone synthase) coding sequences causing ACTH-regulated aldosterone overproduction and hypertension, both readily controlled by low-dose glucocorticoid administration. Expression of aldosterone synthase activity within zona fasciculata (ZF) explained overproduction of hybrid steroids, 18-hydroxy- and 18-oxocortisol. Since 2011, PA-causing germline mutations in another four genes (three associated with FH) have been reported. While three encode cation channels (KCNJ5, CACNA1H and CACNA1D), one encodes an anion channel (CLCN2). FH-III is caused by inheritance of gain-of-function mutations in KCNJ5, encoding an inwardly rectifying potassium channel (GIRK-4). Depending on the exact mutation involved, phenotype varies from very severe (profound PA, hybrid steroid elevation and ZF hyperplasia and requiring bilateral adrenalectomy to control hypertension) to mild (absence of above with PA controllable with spironolactone). Most pedigrees demonstrate early-onset hypertension. Mutations reduce selectivity of GIRK-4 to potassium, permitting entry of sodium into the adrenal cortical cell, which results in cell depolarization and calcium influx, leading to increased expression of CYP11B2 and aldosterone synthesis. A gain-of-function mutation in CACNA1H, encoding a T-type voltage-gated calcium channel, was found in five of 40 subjects with early-onset PA and three relatives with early-onset hypertension (FH-IV). Adrenals appeared normal on imaging. The mutation shifts activation of zona glomerulosa (ZG) cells to a more hyperpolarized potential and slows inactivation, putatively resulting in increased calcium influx and aldosterone production. Germline mutations in CACNA1D, encoding an L-type voltage-gated calcium channel highly expressed in ZG, were identified in two of 100 individuals with early-onset PA. Both occurred de novo, and were associated with seizures and a variety of neurological abnormalities (PASNA). Both mutations cause channel activation at less depolarized membrane potentials, and one nearly abolished channel inactivation. In a large Australian family with FH-II, a mutation was found in CLCN2 encoding a chloride channel, ClC-2. CLCN2 mutations were found in another seven of 80 individuals with early-onset PA. A concurrent report found a CLCN2 mutation in one of 12 subjects with early-onset PA. PA due to CLCN2 mutations responds well to medical treatment. In the adrenal, ClC-2 localizes predominantly to ZG and mutations predispose cell depolarization, leading to calcium influx via activation of voltage-gated calcium channels and increased aldosterone production." @default.
• W4315702932 created "2023-01-12" @default.
• W4315702932 creator A5021228717 @default.
• W4315702932 date "2023-01-01" @default.
• W4315702932 modified "2023-10-01" @default.
• W4315702932 title "S-13-5: UPDATES ON FAMILIAL HYPERALDSOTERONISM" @default.
• W4315702932 doi "https://doi.org/10.1097/01.hjh.0000913072.76354.91" @default.
• W4315702932 hasPublicationYear "2023" @default.
• W4315702932 type Work @default.
• W4315702932 citedByCount "0" @default.
• W4315702932 crossrefType "journal-article" @default.
• W4315702932 hasAuthorship W4315702932A5021228717 @default.
• W4315702932 hasBestOaLocation W43157029321 @default.
• W4315702932 hasConcept C126322002 @default.
• W4315702932 hasConcept C134018914 @default.
• W4315702932 hasConcept C155392382 @default.
• W4315702932 hasConcept C198710026 @default.
• W4315702932 hasConcept C2776292634 @default.
• W4315702932 hasConcept C2777977426 @default.
• W4315702932 hasConcept C2778525890 @default.
• W4315702932 hasConcept C2778736161 @default.
• W4315702932 hasConcept C2780233176 @default.
• W4315702932 hasConcept C2780249997 @default.
• W4315702932 hasConcept C2780902042 @default.
• W4315702932 hasConcept C71315377 @default.
• W4315702932 hasConcept C71924100 @default.
• W4315702932 hasConcept C84393581 @default.
• W4315702932 hasConceptScore W4315702932C126322002 @default.
• W4315702932 hasConceptScore W4315702932C134018914 @default.
• W4315702932 hasConceptScore W4315702932C155392382 @default.
• W4315702932 hasConceptScore W4315702932C198710026 @default.
• W4315702932 hasConceptScore W4315702932C2776292634 @default.
• W4315702932 hasConceptScore W4315702932C2777977426 @default.
• W4315702932 hasConceptScore W4315702932C2778525890 @default.
• W4315702932 hasConceptScore W4315702932C2778736161 @default.
• W4315702932 hasConceptScore W4315702932C2780233176 @default.
• W4315702932 hasConceptScore W4315702932C2780249997 @default.
• W4315702932 hasConceptScore W4315702932C2780902042 @default.
• W4315702932 hasConceptScore W4315702932C71315377 @default.
• W4315702932 hasConceptScore W4315702932C71924100 @default.
• W4315702932 hasConceptScore W4315702932C84393581 @default.
• W4315702932 hasIssue "Suppl 1" @default.
• W4315702932 hasLocation W43157029321 @default.
• W4315702932 hasLocation W43157029322 @default.
• W4315702932 hasOpenAccess W4315702932 @default.
• W4315702932 hasPrimaryLocation W43157029321 @default.
• W4315702932 hasRelatedWork W1969696852 @default.
• W4315702932 hasRelatedWork W1973768362 @default.
• W4315702932 hasRelatedWork W1976214281 @default.
• W4315702932 hasRelatedWork W1976715469 @default.
• W4315702932 hasRelatedWork W1994557505 @default.
• W4315702932 hasRelatedWork W2101834938 @default.
• W4315702932 hasRelatedWork W2152585030 @default.
• W4315702932 hasRelatedWork W2536112776 @default.
• W4315702932 hasRelatedWork W2606853105 @default.
• W4315702932 hasRelatedWork W4284879376 @default.
• W4315702932 hasVolume "41" @default.
• W4315702932 isParatext "false" @default.
• W4315702932 isRetracted "false" @default.
• W4315702932 workType "article" @default.