Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F23%3A10465919" target="_blank" >RIV/00179906:_____/23:10465919 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/23:10465919
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=t2ae_Qw9QU" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=t2ae_Qw9QU</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41588-023-01403-0" target="_blank" >10.1038/s41588-023-01403-0</a>
Alternative languages
Result language
angličtina
Original language name
Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production
Original language description
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. Recurrent somatic mutations altering residues in the transmembrane domain of CADM1 are identified in aldosterone-producing adenomas. Follow-up studies implicate a role of gap junction communication in regulating aldosterone production.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30101 - Human genetics
Result continuities
Project
—
Continuities
—
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Genetics
ISSN
1061-4036
e-ISSN
1546-1718
Volume of the periodical
55
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
1009-1021
UT code for WoS article
001004549100003
EID of the result in the Scopus database
2-s2.0-85161401185