3个常染色体显性遗传多囊肾病家系的遗传学分析

娄桂予; 田向永; 张玉薇; 杨科; 刘红彦; 张晓梅; 曹慧霞; 王斌

doi:10.16016/j.1000-5404.202104203

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3个常染色体显性遗传多囊肾病家系的遗传学分析

基础医学 | 更新时间：2026-01-09

- 3个常染色体显性遗传多囊肾病家系的遗传学分析
- Genetic analysis of 3 pedigrees with autosomal dominant polycystic kidney disease
- 第三军医大学学报 2021年43卷第20期页码：2208-2213
- 作者机构：
  
  1.450002 郑州，河南省人民医院，河南大学人民医院，郑州大学人民医院医学遗传研究所河南省遗传性疾病功能重点实验室
  2.450002 郑州，河南省人民医院，河南大学人民医院，郑州大学人民医院医学遗传研究所泌尿外科
  3.450002 郑州，河南省人民医院，河南大学人民医院，郑州大学人民医院医学遗传研究所肾内科
  4.450002 郑州，河南省人民医院，河南大学人民医院，郑州大学人民医院医学遗传研究所神经外科
- 作者简介：
  
  [ 王斌，E-mail：wb201166@sina.com WANG Bin, E-mail: wb201166@sina.com
- 基金信息：
- DOI：10.16016/j.1000-5404.202104203
  中图分类号： R394.3;R596.1;R692
- 收稿：2021-04-30，
  
  修回：2021-07-06，
  
  纸质出版：2021-10-30
- 稿件说明：
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娄桂予, 田向永, 张玉薇, 等. 3个常染色体显性遗传多囊肾病家系的遗传学分析[J]. 第三军医大学学报, 2021,43(20):2208-2213.

Guiyu LOU, Xiangyong TIAN, Yuwei ZHANG, et al. Genetic analysis of 3 pedigrees with autosomal dominant polycystic kidney disease[J]. Journal of Third Military Medical University, 2021, 43(20): 2208-2213.
娄桂予, 田向永, 张玉薇, 等. 3个常染色体显性遗传多囊肾病家系的遗传学分析[J]. 第三军医大学学报, 2021,43(20):2208-2213. DOI： 10.16016/j.1000-5404.202104203.

Guiyu LOU, Xiangyong TIAN, Yuwei ZHANG, et al. Genetic analysis of 3 pedigrees with autosomal dominant polycystic kidney disease[J]. Journal of Third Military Medical University, 2021, 43(20): 2208-2213. DOI： 10.16016/j.1000-5404.202104203.

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

PKD

1(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。

Abstract

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

G3a

and G5 respectively. The deletion frameshift mutation c.5933delA (p.Asn1978fs)

nonsense heterozygous mutation c.6871C

T (G2291X) and deletion frameshift mutation of c.894_897delCCCT (p.299Sfs*34) in polycystic kidney disease 1 (

PKD

1) 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.5933delA and c.894_897delCCCT are new mutations

and c.6871C>T is a known pathogenic mutation.

关键词

Keywords

references

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