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Mutation analyses by next-generation sequencing and multiplex ligation-dependent probe amplification in Japanese autosomal dominant polycystic kidney disease patients

  • Toshio MochizukiEmail author
  • Atsuko Teraoka
  • Hiroyuki Akagawa
  • Shiho Makabe
  • Taro Akihisa
  • Masayo Sato
  • Hiroshi Kataoka
  • Michihiro Mitobe
  • Toru Furukawa
  • Ken Tsuchiya
  • Kosaku Nitta
Original article
  • 36 Downloads

Abstract

Background

Autosomal dominant polycystic kidney disease (ADPKD), one of the most common hereditary kidney diseases, causes gradual growth of cysts in the kidneys, leading to renal failure. Owing to the advanced technology of next-generation sequencing (NGS), genetic analyses of the causative genes PKD1 and PKD2 have been improved.

Methods

We performed genetic analyses of 111 Japanese ADPKD patients using hybridization-based NGS and long-range (LR)-PCR-based NGS. Additionally, genetic analyses in exon 1 of PKD1 using Sanger sequencing because of an extremely low coverage of NGS and those using multiplex ligation-dependent probe amplification (MLPA) were performed.

Results

The detection rate using NGS for 111 patients was 86.5%. One mutation in exon 1 of PKD1 and five deletions detected by MLPA were identified. When combined, the total detection rate was 91.9%.

Conclusion

Although NGS is useful, we propose the addition of Sanger sequencing for exon 1 of PKD1 and MLPA as indispensable for identifying mutations not detected by NGS.

Keywords

Polycystic kidney disease ADPKD PKD1 PKD2 Next-generation sequencing MLPA 

Notes

Acknowledgements

We express our sincere appreciation to all the patients, collaborating physicians, and other medical staff for their important contributions to the study. This study was supported in part by JSPS KAKENHI Grant Number JP 15K09279 and by a Grant-in-Aid for Intractable Renal Diseases Research, Research on rare and intractable diseases, Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan.

Compliance with ethical standards

Conflict of interest

Toshio Mochizuki and Ken Tsuchiya received Travel fees and honoraria for lectures from Otsuka Pharmaceutical Co. Toshio Mochizuki and Hiroshi Kataoka belong to an endowed department sponsored by Otsuka Pharmaceutical Co, Chugai Pharmaceutical Co, Kyowa Hakko Kirin Co, MSD Co, and JMS Co.

Ethical approval

All procedures performed in this study were approved by the research ethics committee of Tokyo Women’s Medical University (No. 196B) in accordance with the 1964 Helsinki Declaration and its later amendments, or with comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10157_2019_1736_MOESM1_ESM.pdf (96 kb)
Supplementary material 1 (PDF 95 kb)
10157_2019_1736_MOESM2_ESM.pdf (339 kb)
Supplementary material 2 (PDF 338 kb)

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Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  • Toshio Mochizuki
    • 1
    • 2
    Email author
  • Atsuko Teraoka
    • 1
  • Hiroyuki Akagawa
    • 3
  • Shiho Makabe
    • 1
  • Taro Akihisa
    • 1
  • Masayo Sato
    • 1
  • Hiroshi Kataoka
    • 1
    • 2
  • Michihiro Mitobe
    • 1
  • Toru Furukawa
    • 3
    • 4
  • Ken Tsuchiya
    • 5
  • Kosaku Nitta
    • 1
  1. 1.Department of Medicine, Kidney CenterTokyo Women’s Medical UniversityTokyoJapan
  2. 2.Clinical Research Division for Polycystic Kidney Disease, Department of Medicine, Kidney CenterTokyo Women’s Medical UniversityTokyoJapan
  3. 3.Tokyo Women’s Medical University Institute for Integrated Medical Sciences (TIIMS)TokyoJapan
  4. 4.Department of HistopathologyTohoku University Graduate School of MedicineSendaiJapan
  5. 5.Department of Blood Purification, Kidney CenterTokyo Women’s Medical UniversityTokyoJapan

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