一个Liddle综合征家系上皮钠通道基因突变的研究  

Mutation screening of epithelial sodium channel gene in a Liddle's syndrome family

作　　者：王谷亮[1] 张奎星[1] 高平进[1] 韩战营[1] 朱鼎良[1] 孔燕[2] 陆旭辉[2] 郭冀珍[2] 黄薇 

机构地区：[1]上海第二医科大学附属瑞金医院上海市高血压研究所,200025 [2]上海第二医科大学附属瑞金医院上海市高血压研究所高血压科 [3]国家人类基因组南方研究中心

出　　处：《中华肾脏病杂志》2002年第4期247-250,共4页Chinese Journal of Nephrology

基　　金：国家863计划资助项目(102-10-02-03;Z19-01-03-01A)

摘　　要：目的 对1个Liddle综合征家系成员进行基因突变分析。方法 1个3代均有高血压患者的家系中,1例14岁的成员临床诊断为Liddle综合征。抽取所有存活家系成员的外周血基因组DNA,PCR扩增上皮钠通道β亚单位基因(βENaC)和γ亚单位基因(γENaC)第13外显子,产物直接DNA测序进行基因突变检测。结果 βENaC基因第13外显子的DNA经双向测序显示,先证者及另两例家系成员第616号密码子均存在CCC-TCC(Pro-Ser)杂合错义突变,并且第632号密码子存在GAC-CAC(Asp-His)的变异与之连锁。对150例无关个体进行直接测序未发现GAC-CAC变异,证明这是一新的突变。其他家系成员均未发现这一基因突变,另2例基因突变的成员的临床生化检测结果符合Liddle综合征;所有家系成员中未检测到γENaC基因第13外显子的突变。结论 对临床诊断的Liddle综合征患者及其亲属,进行基因突变检测有助于早期筛选出家系中的其他患者。该家系中,第632号密码子检测到一新的突变GAC-CAC(Asp-His),通过表型分析认为这一新突变有可能与Liddle综合征有关。Objective To screen the mutation in P and 7 subunit of epithelial sodium channel (ENaC) gene in the relatives of a patient diagnosed as Liddle's syndrome. Methods In a family of three generations, seven family members were affected with hypertension, among them a girl aged 14 years was diagnosed as Laddie's syndrome and her mother and maternal grandsire died of stroke at thirty-eight years. Peripheral blood samples were collected from all living members of the family and total genomic DNA was prepared for genetic analysis. Polymerase chain reaction (PCR) was used for amplifying the final exon of the β ENaC (codon 513-638) and γ ENaC (codon 524-631 )gene. PCR products were purified and subjected to direct DNA sequencing. Results Genetic analysis of the β ENaC gene revealed a missense mutation of CCC (Pro) to TCC (Ser)at codon 616 in the index case and two other family members. In these three family members, a new variant of GAC (Asp) to CAC(His) at codon 632 was found, which was linked with 616 (Ser) . This variant was not detected by direct sequencing the final exon of β ENaC gene in 150 unrelated subjects. Through clinical examinations and biochemical measurement, thSese two mutation carriers' biochemical characteristics were all concordant with Liddle's syndrome. Neither mutation could be detected in other members of this family. The mutation TGG(Trp)573TAG(Term) of γ ENaC gene could not be found in this family either. Conclusions (1) Screening for specific mutations of ENaC in relatives of patients affected with Liddle's syndrome can be used to identify previously unrecognized cases within families. (2) A new missense mutation in the β ENaC gene is found in this family.

关 键 词：LIDDLE综合征 高血压 上皮钠通道 基因突变 常染色体显性遗传病 

分 类 号：R596.1[医药卫生—内科学]