摘要
目的对3个常染色体显性遗传多囊肾病家系进行基因检测,明确其致病性突变,为防治方法及产前诊断提供指导。方法收集2017-2020年在河南省人民医院泌尿外科就诊的3个多囊肾家系的病史及临床资料;采集家系成员外周血样品提取DNA,利用靶向扩增高通量测序方法对先证者进行检测,筛查可疑致病位点;Sanger测序法对先证者及家系其他成员进行验证及分析,结合生物信息学分析及美国医学遗传与基因组学会制定的基因变异致病性评估标准,分析变异的致病性。结果家系1、2、3先证者超声结果诊断均为多囊肾,临床分期分别为G1、G3a和G5,在PKD1(polycystic kidney disease 1)基因分别发现c.5933delA(p.Asn1978fs)缺失移码突变、c.6871C>T(G2291X)无义杂合突变和c.894_897delCCCT(p.299Sfs*34)缺失移码变异。3个家系的以上变异符合表型-基因型相分离。结论明确了遗传多囊肾病3个家系的致病变异位点,其中c.5933delA和c.894_897delCCCT为新突变,c.6871C>T为已知致病性突变。
Objective To clarify the pathogenic mutations and provide references for prevention and treatment strategies and prenatal diagnosis by gene detection in 3 pedigrees with autosomal dominant polycystic kidney disease(ADPKD).Methods The family history and clinical data of 3 ADPKD pedigrees who admitted to our department of urology during 2017 and 2020 were collected in this study.The peripheral blood samples of these family members were harvested for DNA extraction.Targeted amplification and high-throughput sequencing was used to screen suspected pathogenic mutations in probands,and then these obtained mutations were verified and analyzed in the probands and their family members by Sanger sequencing.The pathogenicity of these mutations was analyzed with bioinformation analysis and the evaluation criteria of the American Society of Medical Genetics.Results Ultrasound examination showed that all the probands from the 3 families had polycystic kidneys,at the clinical stages of G1,G3 a,and G5 respectively.The deletion frameshift mutation c.5933 delA(p.Asn1978 fs),nonsense heterozygous mutation c.6871 C>T(G2291 X)and deletion frameshift mutation of c.894897 delCCCT(p.299 Sfs*34)in polycystic kidney disease 1(PKD1)gene were detected in pedigrees 1,2 and 3,respectively.The above variants in the 3 families were in line with phenotype-genotype separation.Conclusion We identify the pathogenic variants in the 3 pedigrees of hereditary polycystic kidney disease,among which c.5933 delA and c.894897 delCCCT are new mutations,and c.6871 C>T is a known pathogenic mutation.
作者
娄桂予
田向永
张玉薇
杨科
刘红彦
张晓梅
曹慧霞
王斌
LOU Guiyu;TIAN Xiangyong;ZHANG Yuwei;YANG Ke;LIU Hongyan;ZHANG Xiaomei;CAO Huixia;WANG Bin(Institute of Medical Genetics,Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics,Henan Provincial People’s Hospital,People’s Hospital of Henan University,People’s Hospital of Zhengzhou University,Zhengzhou,Henan Province,450002,China;Department of Urology,Henan Provincial People’s Hospital,People’s Hospital of Henan University,People’s Hospital of Zhengzhou University,Zhengzhou,Henan Province,450002,China;Department of Nephrology,Henan Provincial People’s Hospital,People’s Hospital of Henan University,People’s Hospital of Zhengzhou University,Zhengzhou,Henan Province,450002,China;Department of Neurosurgery,Henan Provincial People’s Hospital,People’s Hospital of Henan University,People’s Hospital of Zhengzhou University,Zhengzhou,Henan Province,450002,China)
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2021年第20期2208-2213,共6页
Journal of Third Military Medical University
