论文部分内容阅读
目的在疑诊Liddle’s综合征的家系患者中行基因突变筛查,明确患者的遗传型和表型。方法收集疑诊家系,包括临床资料和静脉血,300例正常健康者作为对照。候选基因为编码肾集合管细胞上皮钠通道(ENaC)β亚单位基因(SCNN1B,NCBI序列号6338),设计引物对SCNN1B所有外显子及其侧翼内含子序列进行基因扫描,聚合酶链反应(PCR)扩增目的片段,双脱氧末段终止法测序。结果发现先证者SCNN1B基因13外显子C1696T突变,其父亲、姐姐也携带同样基因突变,而300例正常对照中未发现此突变。分析提示该突变导致编码蛋白566位出现了编码终止,先证者的表型严重,并且高度类似原发性醛固酮增多症,而家系患者表型较轻,其表型异质性有待明确。结论 SCNN1B C1696T突变可引起编码蛋白R566X突变,从而导致Liddle’s综合征,但携带该突变的患者临床表型存在异质性,并且容易误诊为原发性醛固酮增多症,建议进一步优化原发性醛固酮增多症的诊治流程,并对有条件的患者及早行基因诊断。
Objective To screen gene mutations in pedigree patients with suspected Liddle’s syndrome to identify the patient’s genetic type and phenotype. Methods Suspected pedigrees were collected, including clinical data and venous blood, and 300 normal controls were used as controls. The candidate gene is the gene encoding the epithelial sodium channel (ENaC) β subunit (SCNN1B, NCBI sequence number 6338) of renal collecting duct epithelial cells. The primers were designed to perform gene scanning on all exons of SCNN1B and its flanking intron sequences. Polymerase chain reaction (PCR) amplification of the target fragment, dideoxy end-stop sequencing. The results showed that probands SCNN1B gene 13 exon C1696T mutation, the father, sister also carry the same gene mutation, 300 cases of normal controls did not find this mutation. Analysis suggested that the mutation led to the coding protein 566 termination appeared coding, proband’s phenotype is serious, and highly similar to primary aldosteronism, while the families of patients with mild phenotype, the phenotypic heterogeneity to be determined. CONCLUSION: The SCNN1B C1696T mutation causes the encoded protein R566X mutation leading to Liddle’s syndrome. However, the clinical phenotype of patients with this mutation is heterogeneous and easily misdiagnosed as primary aldosteronism. It is recommended to further optimize the primary aldosteronism Disease diagnosis and treatment process, and conditional patients early gene diagnosis.