Publication year
2013Author(s)
Source
Nature Genetics, 45, 9, (2013), pp. 1055-1060ISSN
Publication type
Article / Letter to editor

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Organization
Radiology
Pathology
Internal Medicine
Journal title
Nature Genetics
Volume
vol. 45
Issue
iss. 9
Page start
p. 1055
Page end
p. 1060
Subject
NCEBP 14: Cardiovascular diseases; ONCOL 3 - Translational research DCN MP - Plasticity and memoryAbstract
At least 5% of individuals with hypertension have adrenal aldosterone-producing adenomas (APAs). Gain-of-function mutations in KCNJ5 and apparent loss-of-function mutations in ATP1A1 and ATP2A3 were reported to occur in APAs. We find that KCNJ5 mutations are common in APAs resembling cortisol-secreting cells of the adrenal zona fasciculata but are absent in a subset of APAs resembling the aldosterone-secreting cells of the adrenal zona glomerulosa. We performed exome sequencing of ten zona glomerulosa-like APAs and identified nine with somatic mutations in either ATP1A1, encoding the Na(+)/K(+) ATPase alpha1 subunit, or CACNA1D, encoding Cav1.3. The ATP1A1 mutations all caused inward leak currents under physiological conditions, and the CACNA1D mutations induced a shift of voltage-dependent gating to more negative voltages, suppressed inactivation or increased currents. Many APAs with these mutations were <1 cm in diameter and had been overlooked on conventional adrenal imaging. Recognition of the distinct genotype and phenotype for this subset of APAs could facilitate diagnosis.
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- Faculty of Medical Sciences [80320]
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