title: Molecular genetics of Liddle's syndrome.
abstract: Liddle's syndrome, an autosomal dominant form of monogenic hypertension, is characterized by salt-sensitive hypertension with early penetrance, hypokalemia, metabolic alkalosis, suppression of plasma rennin activity and aldosterone secretion, and a clear-cut response to epithelial sodium channel (ENaC) blockers but not spironolactone therapy. Our understanding of ENaCs and Na(+) transport defects has expanded greatly over the past two decades and provides detailed insight into the molecular basis of Liddle's syndrome. In this review, we offer an overview of recent advances in understanding the molecular genetics of Liddle's syndrome, involving mutation analysis, molecular mechanisms and genetic testing. The ENaC in the distal nephron is composed of α, β and γ subunits that share similar structures. Mutations associated with Liddle's syndrome are positioned in either β or γ subunits and disturb or truncate a conserved proline-rich sequence (i.e., PY motif), leading to constitutive activation of the ENaC. Genetic testing has made it possible to make accurate diagnoses and develop tailored therapies for mutation carriers.
authors.affiliation: Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Beijing 100037, China.
authors.forename: Kun-Qi
authors.initials: KQ
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Beijing 100037, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Beijing 100037, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Geriatric Cardiology, General Hospital of the Chinese People's Liberation Army, Beijing 100853, China. Electronic address: gaolinggen@163.com.
authors.forename: Ling-Gen
authors.initials: LG
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Beijing 100037, China. Electronic address: zhouxianliang0326@hotmail.com.
authors.forename: Xian-Liang
authors.initials: XL
authors.lastname: Zhou
mesh_terms: D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D005820:Genetic Testing; D006801:Humans; D056929:Liddle Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D008967:Molecular Biology / Q000379:methods*
chemical_list: D053503:Epithelial Sodium Channels
keywords: ENaC; Genetic diagnosis; Liddle's syndrome; Mutation; PY motif