Ma X, Tian Y, Gao Y, Guo X
Department of Endocrinology, First Hospital, Peking University, Beijing 100034, China.
Zhonghua Nei Ke Za Zhi. 2001 Jun;40(6):390-3.
To study the genetic mechanism of Liddle's syndrome in a family and help the diagnosis (specially ante-natal) and treatment of Liddle's syndrome clinically.
(1) Physical examination and measurement of serum potassium, plasma aldosterone and renin activity respectively by biochemical and radioimmunological assays were made for the member of the family. (2) Venous blood samples were collected from the members of the family and total genomic DNA was prepared. One set of specific primers was used for direct polymerase chain reaction, for amplifying C terminus of beta-subunit of epithelial sodium channel (hbetaENaC). Polymerase chain reaction products were subjected to single-strand conformation polymorphism and direct DNA sequence analysis.
A new frameshift mutation (1bp, INS, 600G) of the gene of C terminus of beta-subunit of hbetaENaC was found in the Liddle's syndrome family. This mutation introduced a new stop codon at position 605 and deleted the last 34 normal amino acids from the C teminus of hbeta ENaC. Eight genetically affected subjects had severe hypertension and suppressed levels of plasma aldosterone and plasma renin activity; half of them had hypokalemia.
The frameshift mutation (1bp, INS, 600G) of hbetaENaC gene is the likely cause of Liddle's syndrome in this Chinese family.
研究一个家族中Liddle综合征的遗传机制，为Liddle综合征的临床诊断（尤其是产前诊断）及治疗提供帮助。
（1）对该家族成员进行体格检查，并分别采用生化及放射免疫分析法检测血清钾、血浆醛固酮和肾素活性。（2）采集该家族成员的静脉血样本，制备基因组总DNA。使用一组特异性引物进行直接聚合酶链反应，扩增上皮钠通道β亚基（hβENaC）的C末端。聚合酶链反应产物进行单链构象多态性分析及直接DNA序列分析。
在该Liddle综合征家族中发现了hβENaC基因C末端的一个新的移码突变（1bp，插入，600G）。此突变在第605位引入了一个新的终止密码子，并从hβENaC的C末端缺失了最后34个正常氨基酸。8名受遗传影响的受试者患有严重高血压，血浆醛固酮和血浆肾素活性水平受到抑制；其中一半有低钾血症。
hβENaC基因的移码突变（1bp，插入，600G）可能是这个中国家族中Liddle综合征的病因。
