A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases

Kidney Int. 2018 Aug;94(2):363-371. doi: 10.1016/j.kint.2018.02.027. Epub 2018 May 22.


Molecular diagnosis of inherited kidney diseases remains a challenge due to their expanding phenotypic spectra as well as the constantly growing list of disease-causing genes. Here we develop a comprehensive approach for genetic diagnosis of inherited cystic and glomerular nephropathies. Targeted next generation sequencing of 140 genes causative of or associated with cystic or glomerular nephropathies was performed in 421 patients, a validation cohort of 116 patients with previously known mutations, and a diagnostic cohort of 207 patients with suspected inherited cystic disease and 98 patients with glomerular disease. In the validation cohort, a sensitivity of 99% was achieved. In the diagnostic cohort, causative mutations were found in 78% of patients with cystic disease and 62% of patients with glomerular disease, mostly familial cases, including copy number variants. Results depict the distribution of different cystic and glomerular inherited diseases showing the most likely diagnosis according to perinatal, pediatric and adult disease onset. Of all the genetically diagnosed patients, 15% were referred with an unspecified clinical diagnosis and in 2% genetic testing changed the clinical diagnosis. Therefore, in 17% of cases our genetic analysis was crucial to establish the correct diagnosis. Complex inheritance patterns in autosomal dominant polycystic kidney disease and Alport syndrome were suspected in seven and six patients, respectively. Thus, our kidney-disease gene panel is a comprehensive, noninvasive, and cost-effective tool for genetic diagnosis of cystic and glomerular inherited kidney diseases. This allows etiologic diagnosis in three-quarters of patients and is especially valuable in patients with unspecific or atypical phenotypes.

Keywords: autosomal dominant polycystic kidney disease; ciliopathies; genetic testing; glomerulopathies; inherited kidney diseases; targeted next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cost-Benefit Analysis
  • DNA Mutational Analysis / economics
  • DNA Mutational Analysis / methods
  • Feasibility Studies
  • Female
  • Genetic Testing / economics
  • Genetic Testing / methods*
  • High-Throughput Nucleotide Sequencing / economics
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Infant
  • Infant, Newborn
  • Kidney / pathology
  • Male
  • Middle Aged
  • Mutation
  • Nephritis, Hereditary / diagnosis*
  • Nephritis, Hereditary / epidemiology
  • Nephritis, Hereditary / genetics
  • Nephritis, Hereditary / pathology
  • Phenotype
  • Polycystic Kidney, Autosomal Dominant / diagnosis*
  • Polycystic Kidney, Autosomal Dominant / epidemiology
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / pathology
  • Pregnancy
  • Prenatal Diagnosis / economics
  • Prenatal Diagnosis / methods*
  • Prevalence
  • Young Adult