title: Comprehensive genetic testing approach for major inherited kidney diseases, using next-generation sequencing with a custom panel.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan. tmori.kid@tmd.ac.jp.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Bioinformatics and Genomics, Kanazawa University, Ishikawa, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hosomichi
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Chiga
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Mandai
authors.affiliation: Division of Human Genetics, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakaoka
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan.
authors.forename: Eisei
authors.initials: E
authors.lastname: Sohara
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Okado
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan.
authors.forename: Tatemitsu
authors.initials: T
authors.lastname: Rai
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Division of Human Genetics, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uchida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D040941:Heredity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers
keywords: Comprehensive diagnosis; Custom panel; Inherited kidney diseases; Next-generation sequencing; SPEEDI-KID