Mosaicism for KCNJ5 Causing Early-Onset Primary Aldosteronism due to Bilateral Adrenocortical Hyperplasia.
KCNJ5
blood pressure
familial hyperaldosteronism
genetics
hyperaldosteronism
hypertension
mosaicism
primary aldosteronism
Journal
American journal of hypertension
ISSN: 1941-7225
Titre abrégé: Am J Hypertens
Pays: United States
ID NLM: 8803676
Informations de publication
Date de publication:
22 02 2020
22 02 2020
Historique:
received:
23
07
2019
revised:
19
09
2019
accepted:
18
10
2019
pubmed:
23
10
2019
medline:
22
12
2020
entrez:
23
10
2019
Statut:
ppublish
Résumé
Somatic variants in KCNJ5 are the most common cause of primary aldosteronism (PA). There are few patients with PA in whom the disease is caused by germline variants in the KCNJ5 potassium channel gene (familial hyperaldosteronism type III-FH-III). A 5-year-old patient who developed hypertension due to bilateral adrenocortical hyperplasia (BAH) causing PA had negative peripheral DNA testing for any known genetic causes of PA. He was treated medically with adequate control of his PA but by the third decade of his life, due to worsening renal function, he underwent bilateral adrenalectomy. Focused exome sequencing in multiple nodules of his BAH uncovered a "hot-spot" pathogenic KCNJ5 variant, while repeated Sanger sequencing showed no detectable DNA defects in peripheral blood and other tissues. However, whole exome, "deep" sequencing revealed that 0.23% of copies of germline DNA did in fact carry the same KCNJ5 variant that was present in the adrenocortical nodules, suggesting low level germline mosaicism for this PA-causing KCNJ5 defect. Thus, this patient represents a unique case of BAH due to a mosaic KCNJ5 defect. Undoubtedly, his milder PA compared with other known cases of FH-III, was due to his mosaicism. This case has a number of implications for the prognosis, treatment, and counseling of the many patients with PA due to BAH that are seen in hypertension clinics.
Sections du résumé
BACKGROUND
Somatic variants in KCNJ5 are the most common cause of primary aldosteronism (PA). There are few patients with PA in whom the disease is caused by germline variants in the KCNJ5 potassium channel gene (familial hyperaldosteronism type III-FH-III).
METHODS
A 5-year-old patient who developed hypertension due to bilateral adrenocortical hyperplasia (BAH) causing PA had negative peripheral DNA testing for any known genetic causes of PA. He was treated medically with adequate control of his PA but by the third decade of his life, due to worsening renal function, he underwent bilateral adrenalectomy.
RESULTS
Focused exome sequencing in multiple nodules of his BAH uncovered a "hot-spot" pathogenic KCNJ5 variant, while repeated Sanger sequencing showed no detectable DNA defects in peripheral blood and other tissues. However, whole exome, "deep" sequencing revealed that 0.23% of copies of germline DNA did in fact carry the same KCNJ5 variant that was present in the adrenocortical nodules, suggesting low level germline mosaicism for this PA-causing KCNJ5 defect.
CONCLUSIONS
Thus, this patient represents a unique case of BAH due to a mosaic KCNJ5 defect. Undoubtedly, his milder PA compared with other known cases of FH-III, was due to his mosaicism. This case has a number of implications for the prognosis, treatment, and counseling of the many patients with PA due to BAH that are seen in hypertension clinics.
Identifiants
pubmed: 31637427
pii: 5601961
doi: 10.1093/ajh/hpz172
pmc: PMC8204147
doi:
Substances chimiques
G Protein-Coupled Inwardly-Rectifying Potassium Channels
0
KCNJ5 protein, human
0
Types de publication
Case Reports
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
124-130Subventions
Organisme : Intramural NIH HHS
ID : Z01 HD008720
Pays : United States
Informations de copyright
© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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