ArticleeLife2015
Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
170 citing papers in PubMed, 3 syntheses or guidelines pooled it, 347 citations in OpenAlex.
- Differences in the clinical and hormonal presentation of patients with familial and sporadic primary aldosteronism.Frontiers in endocrinology · 2024Pooled it
- Identification of risk loci for primary aldosteronism in genome-wide association studies.Nature communications · 2022Pooled it
- A systematic review of pathophysiology and management of familial hyperaldosteronism type 1 in pregnancy.Endocrine · 2021Pooled it
- Inter- and intratumoral heterogeneity of aldosterone-producing adenomas: recent advances and clinical implications.Endocrine journal · 2026Review
- Rare germline variants in canonical and candidate genes in apparently sporadic bilateral primary aldosteronism.Journal of the Endocrine Society · 2026Article
- Primary aldosteronism.Nature reviews. Disease primers · 2026Review
- Familial Hyperaldosteronism Type IV (FH-IV)-Clinical Phenotypes, Genetics and Management ofJournal of clinical medicine · 2026Review
- Compound heterozygous variants of CACNA1H change channel properties and contribute to intractable epilepsy with myoclonic-atonic seizures.Journal of human genetics · 2026Article
- Luminal surface proteome of the brain vasculature uncovers blood-brain barrier regulators.Science (New York, N.Y.) · 2026Article
- ClC-2 Contributes to Hypotonicity-Induced Adrenal Aldosterone Secretion.Acta physiologica (Oxford, England) · 2026Article
- Adrenal histologic and genetic characteristics of primary aldosteronism in late adulthood.European journal of endocrinology · 2026Article
- Early-onset hypertension associated with a CACNA1H variant of uncertain significance: a case report and literature review.BMC cardiovascular disorders · 2026Review
- Emerging methods for subtype differentiation in primary aldosteronism.Journal of internal medicine · 2026Review
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- Regulation of Aldosterone Secretion by Substance P and the Neurokinin Type 1 Receptor in Aldosterone-Producing Adenomas.Journal of the American Heart Association · 2026Article
- Osmolarity Controls Oscillatory Calcium Signaling to Reduce Autonomous Aldosterone Production in Zona Glomerulosa Cells.Endocrinology · 2025Article
- Molecular investigation of primary aldosteronism: exploring genetic heterogeneity in understudied populations.Archives of endocrinology and metabolism · 2025Article
- Adrenal causes of endocrine hypertension in childhood or adolescence.Journal of endocrinological investigation · 2025Review
- Two pairs of CACNA1I (CaV3.3) variants with opposite effects on channel function cause neurodevelopmental disorders of varying severity.PLoS genetics · 2025Article
- Review
110 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 10 institutions in 3 countries.
Funding
Abstract
Many Mendelian traits are likely unrecognized owing to absence of traditional segregation patterns in families due to causation by de novo mutations, incomplete penetrance, and/or variable expressivity. Genome-level sequencing can overcome these complications. Extreme childhood phenotypes are promising candidates for new Mendelian traits. One example is early onset hypertension, a rare form of a global cause of morbidity and mortality. We performed exome sequencing of 40 unrelated subjects with hypertension due to primary aldosteronism by age 10. Five subjects (12.5%) shared the identical, previously unidentified, heterozygous CACNA1H(M1549V) mutation. Two mutations were demonstrated to be de novo events, and all mutations occurred independently. CACNA1H encodes a voltage-gated calcium channel (CaV3.2) expressed in adrenal glomerulosa. CACNA1H(M1549V) showed drastically impaired channel inactivation and activation at more hyperpolarized potentials, producing increased intracellular Ca(2+), the signal for aldosterone production. This mutation explains disease pathogenesis and provides new insight into mechanisms mediating aldosterone production and hypertension.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.