ArticleNature genetics2023
Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.
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Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 54 citations in OpenAlex.
- Evaluation of Aldosterone Suppression by Cinnarizine, a Putative Cav1.3 Inhibitor.The Journal of clinical endocrinology and metabolism · 2025Trial
- CXCR4 reduces aldosterone synthesis via regulating CYP11B2 expression.Genes & diseases · 2026Article
- Artificial Gap Junctional Channel Inhibiting the Proliferation of Hepatocellular Carcinoma Cells.Angewandte Chemie (International ed. in English) · 2026Article
- Primary aldosteronism.Nature reviews. Disease primers · 2026Review
- Integrated Transcriptomics Reveals Evolutionary Trajectories and Cell Density-Dependent Mechanisms in Aldosterone-Producing Adenomas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An Anti-Cell Adhesion Molecule 1 Antibody Improves Mite Antigen-Induced Atopic Dermatitis-Like Lesions and Pruritus in NC/Nga Mice.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Article
- Molecular pathology of primary aldosteronism and hypercortisolism: Impact on adrenal surgery.iScience · 2026Review
- Increased Frequency and Distinct Genotypic Patterns of Somatic Aldosterone-Driver Mutations in Aldosterone-Producing Micronodules from Primary Aldosteronism Patients.Endocrine pathology · 2026Article
- Adrenal histologic and genetic characteristics of primary aldosteronism in late adulthood.European journal of endocrinology · 2026Article
- An Integrated Single-Cell and Epigenomic Resource for Comparative Analysis of the Basal Ganglia.bioRxiv : the preprint server for biology · 2026Article
- Emerging methods for subtype differentiation in primary aldosteronism.Journal of internal medicine · 2026Review
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- A novel compound heterozygous mutation inFrontiers in medicine · 2026Article
- tsRNA-25172 inhibits aldosterone secretion in aldosterone-producing adenomas.Endocrine connections · 2025Article
- Somatic Mutations inHypertension (Dallas, Tex. : 1979) · 2025Article
- Review
- Intratumoural aldosterone and CYP11B2 expression levels among different genotypes of aldosterone producing tumours.Endocrine connections · 2025Article
- The relationship between the expression of ACE2 in peripheral blood and the prognosis of patients with adrenal adenoma and hypertension.Hormones (Athens, Greece) · 2025Article
- Speculating suitability of partial adrenalectomy for lateralized primary aldosteronism: With emphasis on partial and complete success as optimistic outcomes.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Sexual dimorphism in benign adrenocortical tumours.European journal of endocrinology · 2025Review
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Authors and funding
43 authors at 20 institutions in 9 countries.
Xilin WuEndocrine Hypertension, Department of Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK.
Elena A B Azizan *Endocrine Hypertension, Department of Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK. elena.azizan@ukm.edu.my.ORCID 0000-0002-5549-4242
Emily Goodchild *Endocrine Hypertension, Department of Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK.
Sumedha Garg *Endocrine Hypertension, Department of Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK.ORCID 0000-0002-4375-8968
Man Hagiyama *Department of Pathology, Faculty of Medicine, Kindai University, Osakasayama, Japan.ORCID 0000-0002-9546-8751
Claudia P Cabrera *NIHR Barts Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.ORCID 0000-0002-2205-5315
Fabio L Fernandes-Rosa *Université Paris Cité, PARCC, Inserm, Paris, France.ORCID 0000-0002-0162-0792
Sheerazed Boulkroun *Université Paris Cité, PARCC, Inserm, Paris, France.ORCID 0000-0002-8796-7534
Jyn Ling KuanCardiovascular Disease Translational Research Programme, Department of Medicine, National University of Singapore, Singapore, Singapore.
Zenia TiangCardiovascular Disease Translational Research Programme, Department of Medicine, National University of Singapore, Singapore, Singapore.
Alessia DavidCentre for Bioinformatics, Department of Life Sciences, Imperial College London, London, UK.ORCID 0000-0001-8687-024X
Masanori MurakamiMedizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich, Germany.ORCID 0000-0002-5541-3502
Charles A MeinBarts and London Genome Centre, School of Medicine and Dentistry, Blizard Institute, London, UK.
Eva WozniakBarts and London Genome Centre, School of Medicine and Dentistry, Blizard Institute, London, UK.
Wanfeng ZhaoDepartment of Histopathology, Addenbrooke's Hospital, Cambridge, UK.
Alison MarkerDepartment of Histopathology, Addenbrooke's Hospital, Cambridge, UK.
Folma BussCambridge Institute for Medical Research, The Keith Peters Building, University of Cambridge, Cambridge, UK.ORCID 0000-0003-4457-3479
Rebecca S SaleebCentre for Microvascular Research, William Harvey Research Institute, Queen Mary University of London, London, UK.
Jackie SalsburyEndocrine Hypertension, Department of Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK.
Yuta TezukaDivision of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Japan.ORCID 0000-0003-1546-6949
Fumitoshi SatohDivision of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Japan.
Kenji OkiDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID 0000-0002-9225-8193
Aaron M UdagerDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Debbie L CohenRenal Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Heather WachtelDepartment of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Peter J KingDepartment of Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK.
William M DrakeNIHR Barts Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Mark GurnellMetabolic Research Laboratories, Welcome Trust-MRC Institute of Metabolic Science, and NIHR Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, Cambridge, UK.ORCID 0000-0001-5745-6832
Jiri Ceral1st Department of Internal Medicine-Cardioangiology, Charles University Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.ORCID 0000-0002-2636-7551
Ales RyskaDepartment of Pathology, Charles University Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Muaatamarulain MustanginDepartment of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Yin Ping WongDepartment of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Geok Chin TanDepartment of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Miroslav Solar1st Department of Internal Medicine-Cardioangiology, Charles University Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Martin ReinckeMedizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich, Germany.ORCID 0000-0002-9817-9875
William E RaineyDivision of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA.
Roger S FooCardiovascular Disease Translational Research Programme, Department of Medicine, National University of Singapore, Singapore, Singapore.ORCID 0000-0002-8079-4618
Yutaka TakaokaDepartment of Computational Drug Design and Mathematical Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyoma, Japan.ORCID 0000-0001-7568-8135
Sandra A MurrayDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Maria-Christina ZennaroUniversité Paris Cité, PARCC, Inserm, Paris, France.ORCID 0000-0001-5449-9191
Felix BeuschleinKlinik für Endokrinologie, Diabetologie und Klinische Ernährung, UniversitätsSpital Zürich (USZ) und Universität Zürich (UZH), Zurich, Switzerland.ORCID 0000-0001-7826-3984
Akihiko ItoDepartment of Pathology, Faculty of Medicine, Kindai University, Osakasayama, Japan.ORCID 0000-0003-1411-4001
Morris J BrownEndocrine Hypertension, Department of Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK. morris.brown@qmul.ac.uk.ORCID 0000-0001-8409-1082
Queen Mary University of London · GBSt Bartholomew's Hospital · GBCharles University · CZInserm · FRNational University of Malaysia · MYNational University of Singapore · SGAddenbrooke's Hospital · GBKindai University · JPLMU Klinikum · DEUniversity of Michigan · USHiroshima University · JPHospital of the University of Pennsylvania · USImperial College London · GBTohoku University · JPTohoku University Hospital · JPUniversity of Cambridge · GBUniversity of Pennsylvania · USUniversity of Pittsburgh · USUniversity of Toyama · JPUniversity of Zurich · CH
Funding
A genotype-phenotype study of germline succinate dehydrogenase pathogenic variantsK08CA270385 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Heather Wachtel · 2022 to 2026
$967kBritish Heart Foundation FS/14/75/31134Department of Health 14/145/09Department of Health BRC-1215-20014Department of Health BRC-1215-20022Medical Research Council MR/S006869/1Medical Research Council MR/S007776/1NCI NIH HHS K08 CA270385Wellcome TrustWellcome Trust 104955/Z/14/Z
Abstract
Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.
Indexed as
Adrenal Cortex NeoplasmsAdrenocortical AdenomaHyperaldosteronismHypertensionAldosteroneCell Adhesion Molecule-1Cytochrome P-450 CYP11B2Gap JunctionsHumansMutationAldosteroneCADM1 protein, humanCell Adhesion Molecule-1Cytochrome P-450 CYP11B2
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