一个常染色体显性遗传性多囊肾病家系PKD1基因的突变研究  

Analysis of PKD1 gene mutation in a family affected with autosomal dominant polycystic kidney disease

作　　者：梅瑾 王敏 王昊 张丽丹 章潘 

机构地区：[1]杭州市妇产科医院(杭州市妇幼保健院),310008 [2]杭州博圣生物科技有限公司,310012

出　　处：《中华医学遗传学杂志》2017年第3期365-368,共4页Chinese Journal of Medical Genetics

基　　金：杭州市重点专病专科项目（20150733Q36）

摘　　要：目的对一个多囊肾病家系进行分子遗传学检测，从基因水平确定其病因，进而分析其临床特点，为遗传咨询和产前诊断提供依据。方法通过临床检查和B超检查结果确诊家系中的3例多囊肾病患者。采用单基因遗传病携带者基因筛查目标捕获测序芯片，通过高通量目标区域捕获测序对家系成员进行突变分析，并在所有家系成员中对检出的遗传变异进行一代测序验证。用SIFT和NCBI等网站对突变进行致病性与保守性分析，预测突变位点的致病性。结果基因芯片捕获测序结果提示先证者和胎儿PKD1基因存在一个尚未报道的新突变c．11333C〉A（p．T3778N），进一步的一代测序结果证实该家系中3例患者均存在同样的突变，而家系中正常成员无此突变。生物信息学分析显示，该错义突变使第3778位上的苏氨酸变为天冬氨酸，该位点区高度保守，突变后可能致病。结论发现了一例PKD1基因的新突变引起的多囊肾病。该家系的新突变可能与常染色体显性多囊肾病的临床表型相关，并在此基础上提供有效的产前基因诊断。Objective To determine the molecular etiology for a family affected with autosomal dominant polycystic kidney disease and provide prenatal diagnosis for the family. Methods Clinical data of the family was collected. Target region sequencing with monogenetic disorders capture array combined with Sanger sequencing and bioinformatics analysis were performed in turn. SIFT and NCB1 were used to evaluate the conservation of the gene and pathogenicity of the identified mutation. Results Target region sequencing has identified a novel c. 11333C〉A （p. T3778N） mutation of the PKD1 gene in the proband and the fetus, which was confirmed by Sanger sequencing in three affected individuals from the family. The same mutation was not detected in healthy members of the pedigree. Bioinformatics analysis suggested that the mutation has caused a likely pathogenic amino acid substitution of Threonine by Aspartic acid, and Clustal analysis indicated that the altered amino acid is highly conserved in mammals. Conclusion A novel mutation of the PKD1 gene has been identified in an affected Chinese family. The mutation is probably responsible for a range of clinical manifestations, for which reliable prenatal diagnosis and genetic counseling may he provided.

关 键 词：多囊肾病 PKD1基因 目标区域捕获测序 

分 类 号：R440[医药卫生—诊断学] R692[医药卫生—临床医学]