对一个Liddle综合征家系临床和上皮细胞钠通道基因突变的研究

A study of mutation(s) of the epithelial sodium channel gene in a Liddle′s syndrome family

目的 通过对 1个Liddle综合征家系的临床表现及其上皮细胞钠通道 β亚单位(hβENaC)基因的研究 ,揭示本家系发病的遗传机制 ,为诊断 (尤其产前诊断 )和治疗提供有力的佐证。方法 (1)对家系成员进行常规体检及血钾、血浆肾素活性、醛固酮水平测定 ;(2 )用单链变构多态性PCR DNA测序等分子生物学方法对hβENaC基因进行分析。结果 在这个Liddle家系中发现了hβENaC基因 (SCNN1B)的 1个移码突变 (1bp ,INS ,6 0 0G) ,8个成员携带此突变基因 ,他们均有严重的高血压、低醛固酮及低肾素活性。 5 0个无关正常人中无突变基因。

Objective 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.Methods (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 β subunit of epithelial sodium channel (hβENaC). Polymerase chain reaction products were subjected to single strand conformation polymorphism and direct DNA sequence analysis.Results A new frameshift mutation (1bp, INS, 600G) of the gene of C terminus of β subunit of hβENaC 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 hβ ENaC. Eight genetically affected subjects had severe hypertension and suppressed levels of plasma aldosterone and plasma renin activity; half of them had hypokalemia.Conclusion The frameshift mutation (1bp, INS, 600G) of hβENaC gene is the likely cause of Liddle′s syndrome in this Chinese family.