BACKGROUNDLiddle's syndrome is a rare autosomal-dominant monogenic form of salt-sensitive hypertension. This study aimed to screen the gene mutation in β and γ subunits of the epithelial sodium channel (ENaC) of a Chinese family with Liddle's syndrome, an autosomal dominant form of hypertension.

METHODSDNA samples from the proband with early-onset, treatment-resistant hypertension and suppressed plasma renin activity were initially screened for mutations in the C-terminal exons of the ENaC β or γ subunit genes, using amplification by polymerase chain reaction and direct DNA sequencing. We also screened the C-terminus of SCNN1B and SCNN1G in family members, and screened for the mutation in 150 controls.

RESULTSGenetic analysis of the β ENaC gene revealed a missense mutation of CCC to TCC at codon 616 in the proband, her mother and her grandmother. One hundred and fifty randomly selected controls had not the mutation, indicating that this is not a common genetic polymorphism. There was no mutation of the γ ENaC gene in any of the individuals examined.

CONCLUSIONSThrough direct DNA sequencing analysis, we established the diagnosis of Liddle's syndrome for the proband and her families, and provided tailored therapies to this abnormality. These results provide further evidence that Pro616Ser is a critical amino acid that has a key role in the inhibition of sodium channel activity.

Adolescent ; DNA Mutational Analysis ; Epithelial Sodium Channels ; genetics ; Female ; Humans ; Liddle Syndrome ; genetics ; Male ; Mutation, Missense ; Pedigree

A 55-year-old man who had been monitored for Liddle syndrome in the nephrology division for 15 years visited again Inje University Sanggye Paik Hospital for a newly developed electrolyte disorder. Because his blood pressure was normal and he showed hypomagnesemia and hypokalemia, a renal clearance test and renal biopsy were conducted for suspected Gitelman syndrome. The patient was diagnosed with Gitelman syndrome, which has been previously reported 12 cases in South Korea. The renal clearance test revealed a disorder of the Na-Cl cotransporter (NCCT) in the distal tubule, while the renal biopsy revealed partial expression of NCCT, typical of Gitelman syndrome. Currently, the patient is being monitored, and is receiving oral administration of calcium and magnesium.
Administration, Oral ; Biopsy ; Blood Pressure ; Calcium ; Clinical Study* ; Gitelman Syndrome* ; Humans ; Hypokalemia ; Korea ; Liddle Syndrome* ; Magnesium ; Middle Aged ; Nephrology ; Solute Carrier Family 12, Member 3

Liddle syndrome is a rare cause of hypokalemic hypertension and caused by renal tubular sodiurn channel defect resulting in excessive sodium absorption, potassium wasting and metabolic alkalosis. Clinically this syndrome resembles the primary aldosteronism, however, aldosterone and renin secretion are markedly suppressed due to chronic state of volume expansion. This syndrome is transmitted in an autosomal dominant pattern. We have experienced a case of Liddle syndrome, a 74 years old female accompanying severe hypokalemia, long-standing hypertension, metabolic alkalosis and suppressed aldosterone and renin level in serum and urine. She had a history of arrhythmia, torsades de pointes, of unknown cause. We believe that the arrhythmia resulted from severe hypokalemia secondary to this syndrome. Two of her siblings died suddenly, probably from cardio-, cerebrovascular accidents. Five her offspring needed to be evaluated for this syndrome due to its autosomal dominant inheritance. Endocrinologically there was no clue for us to seek other diseases of enzyme deficiency needed in aldosterone synthesis. Once the diagnosis of Liddle syndrome was suspecti, we treated her with amiloride 5mg/day for several days. Thereafter metabolic abnormalities including persistent hypertension, not responded to conventional parenteral potassium replacement and antihypertensive drugs, were reversed and normalized until now. We believe that in some of patients of secondary hypertension of unknown cause, Liddle syndrome should be ruled out, and that the incidence of this syndrome has been underes- timated due to lack of suspicion.
Absorption ; Aged ; Aldosterone ; Alkalosis ; Amiloride ; Antihypertensive Agents ; Arrhythmias, Cardiac ; Diagnosis ; Female ; Humans ; Hyperaldosteronism ; Hypertension ; Hypokalemia ; Incidence ; Liddle Syndrome* ; Potassium ; Renin ; Siblings ; Sodium ; Stroke ; Torsades de Pointes* ; Wills

OBJECTIVETo screen the mutation of the beta and gamma subunits of epithelial sodium channel gene SCNN1 in two families with Liddle's syndrome.

METHODSTwo patients clinically diagnosed as Liddle's syndrome and their family members were enrolled. Peripheral blood samples were collected and total genomic DNA was prepared. Polymerase chain reaction (PCR) was used to amplify the exon 13 of the SCNN1B and SCNN1G gene. PCR products were purified and subjected to direct DNA sequencing.

RESULTSA heterozygous nonsense mutation at codon 564 of the SCNN1B gene from CGA(Arg) to stop codon(TGA) was detector in the proband of family 1. More importantly, a novel heterozygous nonsense mutation of CAG(Gln) to stop codon TAG at codon 567 of the SCNN1G gene was detected in the proband and another two members of family 2.

CONCLUSIONScreening for specific mutations of the SCNN1 gene in relatives of patients with Liddle's syndrome can be used to identify the previously unrecognized cases within the family. A new nonsense mutation(Q567X) of the SCNN1G gene is likely the cause of Liddle's syndrome in family 2.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; DNA Mutational Analysis ; Epithelial Sodium Channels ; genetics ; Female ; Humans ; Liddle Syndrome ; genetics ; Male ; Mutation ; genetics ; Pedigree ; Young Adult