Comprehensive genetic testing approach for major inherited kidney diseases, using next-generation sequencing with a custom panel

Clin Exp Nephrol. 2017 Feb;21(1):63-75. doi: 10.1007/s10157-016-1252-1. Epub 2016 Feb 26.

Abstract

Background: Gene identification of hereditary kidney diseases by DNA sequencing is important for precise diagnosis, treatment, and genetic consultations. However, the conventional Sanger sequencing is now practically powerless in the face of ever increasing numbers of reported causative genes of various hereditary diseases. The advent of next-generation sequencing technology has enabled large-scale, genome-wide, simultaneous sequence analyses of multiple candidate genes.

Methods: We designed and verified a comprehensive diagnosis panel for approximately 100 major inherited kidney diseases, including 127 known genes. The panel was named Simple, sPEedy and Efficient Diagnosis of Inherited KIdney Diseases (SPEEDI-KID). We applied the panel to 73 individuals, clinically diagnosed with an inherited kidney disease, from 56 families.

Results: The panel efficiently covered the candidate genes and allowed a prompt and accurate genetic diagnosis. Moreover, 18 unreported mutations suspected as the disease causes were detected. All these mutations were validated by Sanger sequencing, with 100 % concordance.

Conclusion: In conclusion, we developed a powerful diagnostic method, focusing on inherited kidney diseases, using a custom panel, SPEEDI-KID, allowing a fast, easy, and comprehensive diagnosis regardless of the disease type.

Keywords: Comprehensive diagnosis; Custom panel; Inherited kidney diseases; Next-generation sequencing; SPEEDI-KID.

Publication types

  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • DNA Mutational Analysis*
  • Female
  • Gene Expression Profiling*
  • Genetic Association Studies
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Heredity
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Infant
  • Kidney Diseases / diagnosis*
  • Kidney Diseases / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Predictive Value of Tests
  • Reproducibility of Results

Substances

  • Genetic Markers