Hypertension and hyperkalemia associated with Pro701Leu mutation in the NR3C2 gene: A case report

The NR3C2 gene, encoding the mineralocorticoid receptor (MR), harbors over 380 rare coding variants that significantly influence mineralocorticoid homeostasis and disease susceptibility. These variants include both loss-of-function mutations linked to renal pseudohypoaldosteronism type 1 and gain-of-function mutations associated with inherited mineralocorticoid hypertension. This case report describes the clinical features of a previously undocumented NR3C2 mutation, Pro701Leu, in a 60-year-old man presenting with hypertension and hyperkalemia.

A Caucasian male in his early 60 seconds presented with hypertension, hyperkalemia, and a history of chronic obstructive pulmonary disease, treated hepatitis C, bipolar disorder, and long-standing polysubstance use disorder. Despite a family history suggesting Gordon syndrome, genetic testing revealed a unique Pro701Leu mutation in the NR3C2 gene.

The patient was diagnosed with hypertension, hyperkalemia, and a Pro701Leu mutation in the NR3C2 gene. The mutation was identified via next-generation sequencing, revealing a missense mutation with leucine substituted for proline at codon 701 in exon 5.

Initial management included potassium level monitoring and treatment with sodium zirconium cyclosilicate. Despite these measures, hyperkalemia persisted. Furosemide and chlorthalidone were trialed, with chlorthalidone discontinued due to hyponatremia.

The patient's blood pressure was eventually controlled, and potassium levels normalized with continued furosemide treatment. The Pro701Leu mutation represents the first documented case linked to hyperkalemia and hypertension, suggesting an activating mutation in the MR gene.

This case highlights the importance of genetic testing in diagnosing complex cases of hypertension and hyperkalemia. The discovery of the Pro701Leu mutation in the NR3C2 gene underscores the need for further research into its pathophysiological mechanisms and therapeutic implications. Early recognition and tailored treatment can improve patient outcomes in similar cases.