Danial Roshandel1, Maryam Rafati2,3,4, Sara Khorami2, Nima Novin Baheran4, Setareh Jalali1, Razieh Tabatabaie4, Safura Rezai4, Hamid Ahmadieh5, Saeed Reza Ghaffari6,7,8. 1. Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. 3. Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran. 4. Gene Clinic, Tehran, Iran. 5. Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 6. Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. saeed@ghaffari.org. 7. Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran. saeed@ghaffari.org. 8. Gene Clinic, Tehran, Iran. saeed@ghaffari.org.
Abstract
PURPOSE: Retinitis pigmentosa (RP) is the most common hereditary retinal degeneration and an important cause of visual disability worldwide. Rhodopsin gene is one of the most important genes implicated in autosomal dominant RP (ADRP). In this study, we investigated rhodopsin gene mutations in Iranian patients with ADRP. METHODS: Twenty-one patients from 21 unrelated families with a total of 51 affected members were enrolled in this study. After complete history taking, ophthalmic examination and genetic counseling, peripheral blood samples were obtained. Following genomic DNA extraction, all five exons and intron-exon boundaries of RHO gene were sequenced using Sanger method. Interpretation of detected variants was carried out using appropriate databases and bioinformatic tools. Novel variants were screened in 150 unrelated healthy subjects. RESULTS: Results of direct sequencing revealed that five of 21 patients (23.8%) had mutation in the rhodopsin gene. Two of them had previously identified p.P347L mutation, and three had novel variants including p.L95P, p.R177K and p.N310K. None of these novel variants were detected in healthy controls. The p.L95P variant was associated with predominantly inferior retinal involvement. CONCLUSIONS: Our study showed that mutations of the rhodopsin gene are relatively frequent in Iranian patients with ADRP and could be considered in further researches in the future. The novel p.L95P variant may be associated with a specific pattern of retinal degeneration in this population.
PURPOSE:Retinitis pigmentosa (RP) is the most common hereditary retinal degeneration and an important cause of visual disability worldwide. Rhodopsin gene is one of the most important genes implicated in autosomal dominant RP (ADRP). In this study, we investigated rhodopsin gene mutations in Iranian patients with ADRP. METHODS: Twenty-one patients from 21 unrelated families with a total of 51 affected members were enrolled in this study. After complete history taking, ophthalmic examination and genetic counseling, peripheral blood samples were obtained. Following genomic DNA extraction, all five exons and intron-exon boundaries of RHO gene were sequenced using Sanger method. Interpretation of detected variants was carried out using appropriate databases and bioinformatic tools. Novel variants were screened in 150 unrelated healthy subjects. RESULTS: Results of direct sequencing revealed that five of 21 patients (23.8%) had mutation in the rhodopsin gene. Two of them had previously identified p.P347L mutation, and three had novel variants including p.L95P, p.R177K and p.N310K. None of these novel variants were detected in healthy controls. The p.L95P variant was associated with predominantly inferior retinal involvement. CONCLUSIONS: Our study showed that mutations of the rhodopsin gene are relatively frequent in Iranian patients with ADRP and could be considered in further researches in the future. The novel p.L95P variant may be associated with a specific pattern of retinal degeneration in this population.
Authors: Tomas S Aleman; Artur V Cideciyan; Alexander Sumaroka; Elizabeth A M Windsor; Waldo Herrera; D Alan White; Shalesh Kaushal; Anjani Naidu; Alejandro J Roman; Sharon B Schwartz; Edwin M Stone; Samuel G Jacobson Journal: Invest Ophthalmol Vis Sci Date: 2008-04 Impact factor: 4.799
Authors: A V Cideciyan; D C Hood; Y Huang; E Banin; Z Y Li; E M Stone; A H Milam; S G Jacobson Journal: Proc Natl Acad Sci U S A Date: 1998-06-09 Impact factor: 11.205
Authors: M L Naash; N S Peachey; Z Y Li; C C Gryczan; Y Goto; J Blanks; A H Milam; H Ripps Journal: Invest Ophthalmol Vis Sci Date: 1996-04 Impact factor: 4.799
Authors: C Sue Richards; Sherri Bale; Daniel B Bellissimo; Soma Das; Wayne W Grody; Madhuri R Hegde; Elaine Lyon; Brian E Ward Journal: Genet Med Date: 2008-04 Impact factor: 8.822
Authors: C Ziviello; F Simonelli; F Testa; M Anastasi; S B Marzoli; B Falsini; D Ghiglione; C Macaluso; M P Manitto; C Garrè; A Ciccodicola; E Rinaldi; S Banfi Journal: J Med Genet Date: 2005-07 Impact factor: 6.318