Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing

Genet Med. 2015 Apr;17(4):271-8. doi: 10.1038/gim.2014.138. Epub 2014 Nov 6.


Purpose: Inherited retinal dystrophy (IRD) is a leading cause of blindness worldwide. Because of extreme genetic heterogeneity, the etiology and genotypic spectrum of IRD have not been clearly defined, and there is limited information on genotype-phenotype correlations. The purpose of this study was to elucidate the mutational spectrum and genotype-phenotype correlations of IRD.

Methods: We developed a targeted panel of 164 known retinal disease genes, 88 candidate genes, and 32 retina-abundant microRNAs, used for exome sequencing. A total of 179 Chinese families with IRD were recruited.

Results: In 99 unrelated patients, a total of 124 mutations in known retinal disease genes were identified, including 79 novel mutations (detection rate, 55.3%). Moreover, novel genotype-phenotype correlations were discovered, and phenotypic trends noted. Three cases are reported, including the identification of AHI1 as a novel candidate gene for nonsyndromic retinitis pigmentosa.

Conclusion: This study revealed novel genotype-phenotype correlations, including a novel candidate gene, and identified 124 genetic defects within a cohort with IRD . The identification of novel genotype-phenotype correlations and the spectrum of mutations greatly enhance the current knowledge of IRD phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments of IRD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Exome / genetics
  • Female
  • Genetic Association Studies
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense
  • Pedigree
  • Retinal Dystrophies / diagnosis*
  • Retinal Dystrophies / genetics*
  • Retinal Dystrophies / pathology
  • Retinitis Pigmentosa / diagnosis*
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology