Which of the following mutations is implicated in Liddle syndrome, a rare form of inherited hypertension?

MP NHM CHO-2024 (Shift-1)

Pathology & Genetics

Easy

Appeared in: MP NHM CHO-2024 (Shift-1)

Explanation

Liddle syndrome is a rare, inherited form of high blood pressure.
It is caused by a 'gain-of-function' mutation in the SCNN1B or SCNN1G gene.
These genes provide instructions for making parts of the epithelial sodium channel (ENaC) in the kidneys.
The mutation makes the ENaC channel overactive, causing the kidneys to retain too much sodium and water, which raises blood pressure.
This process also leads to the excessive loss of potassium in the urine, resulting in low blood potassium levels (hypokalemia).

Option A: This gene, NR3C2, codes for the mineralocorticoid receptor. Its mutations are associated with other conditions like pseudohypoaldosteronism type 1 (salt-wasting) or a different form of hypertension, not Liddle syndrome.
Option C: The ACE gene is crucial for the Renin-Angiotensin-Aldosterone System (RAAS) but is not the site of the primary genetic defect in Liddle syndrome, which is a channelopathy independent of RAAS.
Option D: The AGTR1 gene codes for the angiotensin II receptor. Like ACE, it is a key part of the RAAS pathway, which is characteristically suppressed in Liddle syndrome, not the cause of it.

Visual 1: Diagram: A diagram of the renal collecting duct cell showing the over-activation of the Epithelial Sodium Channel (ENaC) in Liddle syndrome. The visual should illustrate increased Na+ reabsorption into the blood and increased K+ secretion into the urine.

Clinical Relevance

Nursing practice connection: Knowing Genetic basis of monogenic hypertension, specifically Liddle syndrome helps nurses interpret findings accurately and avoid errors in routine assessment, medication administration, and patient teaching.
The hallmark of Liddle syndrome is the clinical picture of hyperaldosteronism (hypertension, hypokalemia) but with suppressed plasma renin and aldosterone levels. This is a key diagnostic differentiator.
Understanding this distinction is vital for treatment. Aldosterone antagonists like spironolactone are ineffective because aldosterone levels are already low. The correct treatment targets the faulty channel directly with ENaC blockers like amiloride or triamterene.
Nurses should monitor for signs of hypokalemia, such as muscle weakness, cramps, and cardiac arrhythmias, in patients with suspected or confirmed Liddle syndrome.

How to Approach the Question

First, identify the key terms in the question: 'Liddle syndrome' and 'mutation'. This indicates the question is asking for the specific genetic cause of this disease.
Recall that Liddle syndrome is a form of monogenic hypertension related to abnormal kidney function.
Evaluate the options. The SCNN1B gene is associated with a sodium channel. The other genes (NR3C2, ACE, AGTR1) are related to the mineralocorticoid receptor or the Renin-Angiotensin-Aldosterone System (RAAS).
Remember that Liddle syndrome is a 'channelopathy'—a disease of an ion channel. This points directly to the gene encoding that channel.
Differentiate Liddle syndrome's pathophysiology (overactive ENaC, low renin/aldosterone) from conditions involving the RAAS (where renin/aldosterone would be high or inappropriately normal). This confirms that the SCNN1B mutation is the correct choice.

Concept Tested & Keywords

Concept Tested: Genetic basis of monogenic hypertension, specifically Liddle syndrome.
Stem keywords: Liddle syndrome, inherited hypertension, mutation
Lead-in keywords: Which
Negative lead-in flag: false

QLr--Uqv0mKtMMA_JeTwBt