Wang Weiqing, Zhou Weiwei, Jiang Lei, Cui Bin, Ye Lei, Su Tingwei, Wang Jiguang, Li Xiaoying, Ning Guang
Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, P R China.
Endocrine. 2006 Jun;29(3):385-90. doi: 10.1385/ENDO:29:3:385.
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.
利德尔综合征是一种与远曲小管钠重吸收异常相关的疾病，以罕见的常染色体显性性状遗传。它由SCNN1B或SCNN1C基因突变引起，这些突变会截断上皮钠通道（ENaC）β和γ亚基的细胞质羧基末端。对一个患有利德尔综合征的中国家庭的ENaC进行基因分析发现，SCNN1B的P616H与该表型共聚集，而在100名无关个体中未检测到该变体。在该家庭的所有成员中均未检测到γ ENaC的突变。P616H位于βENaC保守的富含脯氨酸的PY基序中。PY基序可与Nedd4中的WW结构域相互作用并影响ENaC的活性。结构生物信息学分析证实，与野生型ENaC相比，Liddle-ENaC（P616H）中Nedd4与ENaC之间的功能相互作用减弱。总之，P616H可能是该家庭体征和症状的潜在机制。
