Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy

Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.


Inherited retinal diseases (IRDs) are a common cause of visual impairment. IRD covers a set of genetically highly heterogeneous disorders with more than 150 genes associated with one or more clinical forms of IRD. Molecular genetic diagnosis has become increasingly important especially due to expanding number of gene therapy strategies under development. Next generation sequencing (NGS) of gene panels has proven a valuable diagnostic tool in IRD. We present the molecular findings of 677 individuals, residing in Denmark, with IRD and report 806 variants of which 187 are novel. We found that deletions and duplications spanning one or more exons can explain 3% of the cases, and thus copy number variation (CNV) analysis is important in molecular genetic diagnostics of IRD. Seven percent of the individuals have variants classified as pathogenic or likely-pathogenic in more than one gene. Possible Danish founder variants in EYS and RP1 are reported. A significant number of variants were classified as variants with unknown significance; reporting of these will hopefully contribute to the elucidation of the actual clinical consequence making the classification less troublesome in the future. In conclusion, this study underlines the relevance of performing targeted sequencing of IRD including CNV analysis as well as the importance of interaction with clinical diagnoses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Denmark
  • Exons / genetics
  • Eye Proteins / genetics
  • Female
  • Genetic Counseling / methods
  • Genetic Predisposition to Disease*
  • Genetic Testing / methods*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Mutation
  • Retinal Dystrophies / blood
  • Retinal Dystrophies / diagnosis
  • Retinal Dystrophies / genetics*
  • Young Adult


  • EYS protein, human
  • Eye Proteins
  • Microtubule-Associated Proteins
  • RP1 protein, human