Comprehensive Genomic Approach to Inherited Retinal Dystrophies using Next Generation Sequencing


Principal Investigator: SR Ghaffari

Principal associate Investigator: M Rafati


  • Phase 1 (2010-2012): Targeted capture sequencing of selected families with high score of autosomal recessive RP
  • Among analyzed pedigrees, 9 families were selected in the first phase of the project for genetic investigations using next generation sequencing
  • Through a collaborative project with “Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, a stepwise approach was applied to these families.
  • The affected individuals were screened for known mutations implicated in RP and Leber Congenital Amaurosis (LCA) using arrayed primer extension (APEX) technology. Firstly, 594 known mutations in 19 autosomal recessive RP (arRP) genes were studied. Subsequently, 641 reported mutations in 13 LCA genes were investigated.
  • No mutation was detected in the first part of the study which investigated more than 1500 known mutations in arRP and LCA. It showed the different pattern of mutations in Iranian patients in comparison with other populations.
  • In the second phase, targeted capture Next Generation Sequencing detected 7 mutations among 9 families with an overall mutation detection rate of 77.7%. Among mutations found, 85.7% (6/7) were novel.
  • In summary, our findings showed that due to the high prevalence of novel mutations (85%) in Iranian RP patients, routine investigation of known mutations by microarray-based techniques would fail to detect pathogenic mutations in these patients. These findings led therefore to the recommendation of a different diagnostic approach to such patients which skips this part of conventional approach to RP patients at that time. Moreover, our study showed the usefulness of next generation sequencing to increase the diagnostic yield in RP patients, especially when copy number variation (CNV) analysis was performed on NGS data.



Phase 2 (2013-Present): Target sequencing of patients with inherited retinal dystrophies using Ion Ampliseq Ophthalmology panel (316 genes) followed by whole exome sequencing

Comprehensive clinical data, pedigrees and Blood samples of >900 families with “Inherited retinal dystrophies” has been collected till now (highly selected families with AR/AD/XL inheritance) and target sequencing is underway.

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