Back to Search
Start Over
KCNJ5 mutations in European families with nonglucocorticoid remediable familial hyperaldosteronism
- Source :
- Hypertension 59, 235-240 (2012), Hypertension; Vol 59
- Publication Year :
- 2012
- Publisher :
- Lippincott Williams & Wilkins, 2012.
-
Abstract
- Primary aldosteronism is the most frequent cause of endocrine hypertension. Three forms of familial hyperaldosteronism (FH) have been described, named FH-I to -III. Recently, a mutation of KCNJ5 has been shown to be associated with FH-III, whereas the cause of FH-II is still unknown. In this study we searched for mutations in KCNJ5 in 46 patients from 21 families with FH, in which FH-I was excluded. We identified a new germline G151E mutation in 2 primary aldosteronism–affected subjects from an Italian family and 3 somatic mutations in aldosterone-producing adenomas, T158A described previously as a germline mutation associated with FH-III, and G151R and L168R both described as somatic mutations in aldosterone-producing adenoma. The phenotype of the family with the G151E mutation was remarkably milder compared with the previously described American family, in terms of both clinical and biochemical parameters. Furthermore, patients with somatic KCNJ5 mutations displayed a phenotype indistinguishable from that of sporadic primary aldosteronism. The functional characterization of the effects of the G151E mutation in vitro showed a profound alteration of the channel function, with loss of K + selectivity, Na + influx, and membrane depolarization. These alterations have been postulated to be responsible for voltage gate Ca 2+ channel activation, increase in cytosolic calcium, and stimulation of aldosterone production and adrenal cell proliferation. In conclusion, we describe herein a new mutation in the KCNJ5 potassium channel associated with FH-III, responsible for marked alterations of channel function but associated with a mild clinical and hormonal phenotype.
- Subjects :
- Adult
Male
medicine.medical_specialty
Familial hyperaldosteronism
hypertension
030209 endocrinology & metabolism
030204 cardiovascular system & hematology
medicine.disease_cause
Germline
White People
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Primary aldosteronism
Germline mutation
Internal medicine
KCNJ5
Hyperaldosteronism
Internal Medicine
medicine
Humans
Treatment Failure
Glucocorticoids
Mutation
Aldosterone
biology
Middle Aged
medicine.disease
Phenotype
Pedigree
Europe
Endocrinology
chemistry
G Protein-Coupled Inwardly-Rectifying Potassium Channels
biology.protein
familial hyperaldosteronism
endocrine hypertension
primary aldosteronism
aldosterone
Female
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Hypertension 59, 235-240 (2012), Hypertension; Vol 59
- Accession number :
- edsair.doi.dedup.....765a71477188696c10d35612b7ebb819