Liddle syndrome misdiagnosed as primary aldosteronism is caused by inaccurate aldosterone-rennin detection while a novel SCNN1G mutation is discovered

Figures & data

Figure 1. Sanger sequencing the results of the proband and her parents. RefSeq: National Centre for Biotechnology Information Reference Sequences.

Table 1. Clinical and biochemical characters of the family members.

Subjects	Gender	Consanguinity	c.1729 C > T	HBP	Onset	BP^b	K+	Aldosteron^dd^dd	Renin^d	ARR^d ddddddd】d	Aldosteron^e	Renine^e	ARR
	M/F	Y/N	Y/N	Y/N	Age^a	mmHg	mmol/L	4-31 ng/dl	4-38ng/l	<3.8这些这些	2.5-39 ng/dl	4.4-46.1µIU/ml
II-6	F	Y	Y	Y	48	160/90	3.0	13.62	0.98	13.9	3.31	0.98	3.4
III-7	F	Y	Y	Y	30	140/97	4.1^c	12.4	0.99	12.5	3.08		3.1
III-8	M	Y	Y	Y	20	170/100	3.4	12.25	0.45	27.2	2.67	1.37	1.9
III-14	M	Y	Y	Y	17	189/118	3.1	12.62	0.78	16.2	1.07	1.49	0.7
IV-3	F	Y	Y	Y	17	144/90	4.0^c	14.10	0.58	24.3	1.77	<0.5
IV-6	F	Y	Y	Y	12	156/118	2.6	23.28	0.29	80.3	2.62	<0.5
III-4	F	Y		Y	47	unknown	3.5	14.94	0.86	17.4	13.6	4.45	3.1
II-1	M	Y	Y	Y	64	150/100	4.2	11.81	0.15	78.7	4.05	3.82	1.1
III-17	F	Y	Y	Y	23	154/93	3.6	56.05	0.29	193.3	4.25		14.7
III-2	F	Y	Y	N	/	/	4.4	12.77	0.11	116.1	2.99	12.15	0.2
IV-2	M	Y		N	/	/	4.2	14.02	0.93	15.08	4.69	4.88	1
II-2	F	N		Y	45	162/98	4.6	15.39	0.62	24.8	–	–	–
II-9	M	N	N	Y	40	166/91	4.2	13.22	0.36	36.7	–	–	–
III-3	M	N		Y	49	156/102	4.4	20.07	1.17	17.2	13.5	18.38	0.7
II-5	M	N		N	/	/	4.3	17.28	1.24	13.9	7.27	6.58	1.1
III-6	M	N		N	/	/	4.6	14.92	1.62	9.20	6.0	18.98	0.3
III-15	F	N	N	N	/	/	4.4	17.13	0.36	47.6	20.4	5.23	3.9

^a onset age of hypertension; ^b highest blood pressure ever recorded; ^c on oral potassium treatment; ^d tested using test kit A; ^e tested using test kit B.

HBP, hypertension; K+, serum potassium; ARR, aldosterone to renin ration; subjects II-1, II-2, III-4, III-8 on the treatment of angiotensin receptor blocker (ARB); subject III-17 on angiotensin-converting enzyme inhibitor (ACEI); subject III-14 on ARB and spironolactone, II-2, III-3 on calcium channel antagonist.

Figure 2. Family pedigree. The black arrow indicates the proband; Black filled symbols: subjects with hypertension. Empty symbols: without hypertension. Seventeen family members are further included in this study：II-1, II-2, II-5, II-6, II-9, III-2, III-3, III-4, III-6, III-7, III-8, III-14, III-15, III-17, IV-2, IV-3, IV-6; Eleven subjects accepted gene test: II-1, II-6, II-9, III-2, III-7, III-8, III-14, III-15, III-17, IV-3, IV-6; Slash indicates passed away due to cerebrovascular accident.

Figure 3. Aldosterone levels were tested by kits A (

) and kit B (

) among family members. *Patient with Liddle syndrome diagnosed with a gene test.

Figure 4. ARR and renin levels were tested with different test kits among family members. Renin is detected below the lower limit of the detection range（less than 0.8 ng/l for patients IV-3 and IV-6) in kit B which is marked at the lower limit of the detection range, so the ARR ratio of patients IV-3 and IV-6 in kit B is not calculated.