Liddle综合征的基因诊断(附4例同胞兄弟上皮钠通道基因突变分析)

The diagnosis of Liddle′s syndrome by genetic analysis of the β subunit of epithelial sodium channel-a report of 4 affected siblings

目的 Liddle综合征家系成员的基因突变分析。方法 一家系三代 4例同胞兄弟均患高血压 ,其中 2例经临床检查诊断为Liddle综合征。抽取三代所有成员的基因组DNA ,用PCR法扩增上皮钠通道β及γ亚单位 ( βENaC ,γENaC)第 13外显子 ,直接DNA测序法进行基因突变检测。 结果 βENaC基因第 13外显子的DNA测序结果显示 ,4例患病同胞兄弟在该外显子的 616号密码子均存在CCC→CTC错义突变 ,家系中其他成员均未发现基因突变。γENaC基因测序未发现突变。结论 同一个家系中的 4例高血压同胞检出 βENaC基因突变 ,在基因水平上确诊为Liddle综合征。

Objective To screen the gene mutation in β and γ subunit of the epithelial sodium channel(ENaC) in a family with patients clinically diagnosed as Liddle′s syndrome. Methods Four siblings from a family of three generations suffered from severe hypertension and two of them were previously diagnosed as Liddle′s syndrome by the evidences of clinical examinations. Peripheral blood samples from all members of the family were collected and total genomic DNA was prepared for genetic analysis. Polymerase chain reaction(PCR) was used for amplifying exon 13 in the β ENaC(codon 513-673) and the γ ENaC (codon 503-632) gene. PCR products were purified and subjected to a direct DNA sequence analysis. Results Genetic analysis of β ENaC gene revealed a missense mutation of pro(CCC) to Leu (CTC) at codon 616 in four siblings. No mutation at γ ENaC could be detected in all members of this family. Conclusion Analysis of the gene encoding β ENaC identified a mutation at codon 616. A direct DNA sequencing analysis diagnosed Liddle′s syndrome in four siblings at gene level.