Genetic epidemiology of inherited retinal diseases in a large patient cohort followed at a single center in Italy

Sci Rep. 2022 Dec 2;12(1):20815. doi: 10.1038/s41598-022-24636-1.


Inherited retinal diseases (IRDs) are the leading cause of vision loss in the working-age population. We performed a retrospective epidemiological study to determine the genetic basis of IRDs in a large Italian cohort (n = 2790) followed at a single referral center. We provided, mainly by next generation sequencing, potentially conclusive molecular diagnosis for 2036 patients (from 1683 unrelated families). We identified a total of 1319 causative sequence variations in 132 genes, including 353 novel variants, and 866 possibly actionable genotypes for therapeutic approaches. ABCA4 was the most frequently mutated gene (n = 535; 26.3% of solved cases), followed by USH2A (n = 228; 11.2%) and RPGR (n = 102; 5.01%). The other 129 genes had a lower contribution to IRD pathogenesis (e.g. CHM 3.5%, RHO 3.5%; MYO7A 3.4%; CRB1 2.7%; RPE65 2%, RP1 1.8%; GUCY2D 1.7%). Seventy-eight genes were mutated in five patients or less. Mitochondrial DNA variants were responsible for 2.1% of cases. Our analysis confirms the complex genetic etiology of IRDs and reveals the high prevalence of ABCA4 and USH2A mutations. This study also uncovers genetic associations with a spectrum of clinical subgroups and highlights a valuable number of cases potentially eligible for clinical trials and, ultimately, for molecular therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Eye Proteins / genetics
  • Humans
  • Italy / epidemiology
  • Membrane Proteins / genetics
  • Molecular Epidemiology
  • Nerve Tissue Proteins
  • Retina
  • Retinal Diseases* / epidemiology
  • Retinal Diseases* / genetics
  • Retrospective Studies


  • RPGR protein, human
  • Eye Proteins
  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters
  • CRB1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins

Supplementary concepts

  • Usher syndrome, type 2A