A Novel Frameshift Mutation of SCNN1G Causing Liddle Syndrome with Normokalemia.
Adolescent
Aged
Amiloride
/ therapeutic use
Antihypertensive Agents
/ therapeutic use
Biomarkers
/ blood
Blood Pressure
Child
Drug Combinations
Epithelial Sodium Channels
/ genetics
Female
Frameshift Mutation
Genetic Predisposition to Disease
Heredity
Humans
Hydrochlorothiazide
/ therapeutic use
Hypertension
/ drug therapy
Liddle Syndrome
/ blood
Male
Middle Aged
Pedigree
Phenotype
Potassium
/ blood
Treatment Outcome
Young Adult
SCNN1G gene
Frameshift mutation
Liddle syndrome
Normokalemia
blood pressure
hypertension
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:
17 07 2019
17 07 2019
Historique:
received:
20
02
2019
revised:
13
03
2019
accepted:
09
04
2019
pubmed:
13
4
2019
medline:
28
7
2020
entrez:
13
4
2019
Statut:
ppublish
Résumé
Liddle syndrome (LS) is an autosomal dominant disorder caused by single-gene mutations of the epithelial sodium channel (ENaC). It is characterized by early-onset hypertension, spontaneous hypokalemia and low plasma renin and aldosterone concentrations. In this study, we reported an LS pedigree with normokalemia resulting from a novel SCNN1G frameshift mutation. Peripheral blood samples were collected from the proband and eight family members for DNA extraction. Next-generation sequencing and Sanger sequencing were performed to identify the SCNN1G mutation. Clinical examinations were used to comprehensively evaluate the phenotypes of two patients. Genetic analysis identified a novel SCNN1G frameshift mutation, p.Arg586Valfs*598, in the proband with LS. This heterozygous frameshift mutation generated a premature stop codon and deleted the vital PY motif of ENaC. The same mutation was present in his elder brother with LS, and his mother without any LS symptoms. Biochemical examination showed normokalemia in the three mutation carriers. The mutation identified was not found in any other family members, 100 hypertensives, or 100 healthy controls. Our study identified a novel SCNN1G frameshift mutation in a Chinese family with LS, expanding the genetic spectrum of SCNN1G. Genetic testing helped us identify LS with a pathogenic mutation when the genotypes and phenotype were not completely consistent because of the hypokalemia. This case emphasizes that once a proband is diagnosed with LS by genetic testing, family genetic sequencing is necessary for early diagnosis and intervention for other family members, to protect against severe cardiovascular complications.
Sections du résumé
BACKGROUND
Liddle syndrome (LS) is an autosomal dominant disorder caused by single-gene mutations of the epithelial sodium channel (ENaC). It is characterized by early-onset hypertension, spontaneous hypokalemia and low plasma renin and aldosterone concentrations. In this study, we reported an LS pedigree with normokalemia resulting from a novel SCNN1G frameshift mutation.
METHODS
Peripheral blood samples were collected from the proband and eight family members for DNA extraction. Next-generation sequencing and Sanger sequencing were performed to identify the SCNN1G mutation. Clinical examinations were used to comprehensively evaluate the phenotypes of two patients.
RESULTS
Genetic analysis identified a novel SCNN1G frameshift mutation, p.Arg586Valfs*598, in the proband with LS. This heterozygous frameshift mutation generated a premature stop codon and deleted the vital PY motif of ENaC. The same mutation was present in his elder brother with LS, and his mother without any LS symptoms. Biochemical examination showed normokalemia in the three mutation carriers. The mutation identified was not found in any other family members, 100 hypertensives, or 100 healthy controls.
CONCLUSIONS
Our study identified a novel SCNN1G frameshift mutation in a Chinese family with LS, expanding the genetic spectrum of SCNN1G. Genetic testing helped us identify LS with a pathogenic mutation when the genotypes and phenotype were not completely consistent because of the hypokalemia. This case emphasizes that once a proband is diagnosed with LS by genetic testing, family genetic sequencing is necessary for early diagnosis and intervention for other family members, to protect against severe cardiovascular complications.
Identifiants
pubmed: 30977777
pii: 5448914
doi: 10.1093/ajh/hpz053
pmc: PMC6636789
doi:
Substances chimiques
Antihypertensive Agents
0
Biomarkers
0
Drug Combinations
0
Epithelial Sodium Channels
0
SCNN1G protein, human
0
Hydrochlorothiazide
0J48LPH2TH
amiloride, hydrochlorothiazide drug combination
68529-45-3
Amiloride
7DZO8EB0Z3
Potassium
RWP5GA015D
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
752-758Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.
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