title: Mutation analysis of SCNN1B in a family with Liddle's syndrome.
abstract: Liddle's syndrome has been known as a disorder associated with abnormal sodium reabsorption in the distal tubule and transmitted as a rare autosomal dominant trait. It is caused by mutations in the SCNN1B or SCNN1C gene, which truncate the cytoplasmic carboxyl terminus of the beta and gamma subunit of the epithelial sodium channel (ENaC). Genetic analysis of ENaC in a Chinese family with Liddle's syndrome revealed P616H of SCNN1B coaggregated with the phenotype, while this variant was not detected in 100 unrelated subjects. No mutation at gamma ENaC could be detected in all members of the family. P616H is located in the conserved proline-rich PY motif of the betaENaC. The PY motif can interact with the WW domain in Nedd4 and affect the activity of ENaC. Structural bioinformatics analysis confirmed that the functional interaction between Nedd4 and ENaC reduces in Liddle-ENaC (P616H) when compared with wild-type ENaC. In summary, P616H may be an underlying mechanism for the signs and symptoms of this family.
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, P R China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.forename: Tingwei
authors.initials: T
authors.lastname: Su
authors.forename: Jiguang
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020816:Amino Acid Motifs; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D053503:Epithelial Sodium Channels; D005190:Family; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D010375:Pedigree; D017434:Protein Structure, Tertiary; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
chemical_list: D053503:Epithelial Sodium Channels; C507048:SCNN1B protein, human; D015222:Sodium Channels