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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 analyze the gene mutation in a member of Liddle syndrome family. Methods One pedigree with three generations of hypertensive patients was diagnosed as Liddle syndrome by a 14-year-old member. Peripheral blood genomic DNA was extracted from all surviving pedigree members. The 13 exons of βENaC and γENaC were amplified by polymerase chain reaction (PCR), and the products were directly sequenced for gene mutation detection. Results The DNA of exon 13 of βENaC gene was bi-directionally sequenced. The heterozygous missense mutations of CCC-TCC (Pro-Ser) were found in probands and codons 616 of the other two families. Variants of the GAC-CAC (Asp-His) exist in the subfamily. No direct GAC-CAC mutation was found in 150 unrelated individuals, demonstrating that this is a new mutation. Other members of the family members did not find this gene mutation, the other two cases of mutations in the clinical biochemical test results in line with Liddle syndrome; all members of the family did not detect γENaC gene mutation in exon 13. Conclusion The detection of gene mutations in clinically diagnosed patients with Liddle syndrome and their relatives is helpful for the early screening of other patients in the family. In this family, a new mutation, GAC-CAC (Asp-His), was detected at codon 632 and this new mutation is thought to be associated with Liddle syndrome by phenotypic analysis.