title: Liddle syndrome in a Serbian family and literature review of underlying mutations.
abstract: Severe and reproducible low-renin hypertension responsive to salt restriction and amiloride-thiazide therapy in a 13-year-old otherwise asymptomatic boy suggested Liddle syndrome. This assumption was strengthened by a positive family history of hypertension poorly responsive to conventional treatment or sudden deaths under 40 years of age in four generations. DNA analysis of the beta and gamma subunits of the epithelial sodium channel revealed a heterozygous mutation c.C1852T (p.Pro618Ser) in the SCNN1B gene in the patient and in both his hypertensive mother and uncle. A PubMed search revealed 21 different disease-causing mutations reported to date, all but two clustering in the cytoplasmic C-terminal regions of either beta (16 mutations) or gamma (5) subunit, leading to a three- to eightfold increase in the amiloride-sensitive sodium current. Inter- and intrafamilial variability in both hypertension and hypokalemia were disclosed, which may not be obligatory among the subjects carrying a Liddle mutation.
  
  
  CONCLUSIONS
  Liddle syndrome should be considered as a cause of hypertension in children or adolescents particularly with suppressed renin activity. Early diagnosis and appropriately tailored treatment avoid complications of long-term unrecognized or inappropriately managed hypertension.
authors.affiliation: Medical Faculty, University of Belgrade, Belgrade, Serbia. maloun@eunet.rs
authors.forename: Radovan
authors.initials: R
authors.lastname: Bogdanović
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kuburović
authors.forename: Nataša
authors.initials: N
authors.lastname: Stajić
authors.forename: Sadaf S
authors.initials: SS
authors.lastname: Mughal
authors.forename: Alina
authors.initials: A
authors.lastname: Hilger
authors.forename: Sanja
authors.initials: S
authors.lastname: Ninić
authors.forename: Sergej
authors.initials: S
authors.lastname: Prijić
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
mesh_terms: D000293:Adolescent; D000328:Adult; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D056929:Liddle Syndrome / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D017354:Point Mutation; D055771:Serbia
chemical_list: D053503:Epithelial Sodium Channels; D005819:Genetic Markers; C507048:SCNN1B protein, human