Maryam Beheshtian1, Samira Saee Rad2, Mojgan Babanejad1, Marzieh Mohseni1, Hassan Hashemi3, Arash Eshghabadi3, Fedra Hajizadeh3, Mohammad Reza Akbari4, Kimia Kahrizi1, Mohammad Riazi Esfahani3, Hossein Najmabadi5. 1. Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. 2. Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran, Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran. 3. Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran. 4. Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON, Canada, Canada and Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 5. Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. hnajm12@yahoo.com.
Abstract
BACKGROUND: Non-syndromic autosomal recessive Retinitis Pigmentosa (arRP) is a highly heterogeneous genetic visual disorder with a large number of causative genes. We aimed to determine the power of Whole Exome Sequencing (WES) in the identification of the genes responsible for non-syndromic arRP among Iranian patients. METHODS: We used WES, followed by the Sanger sequencing to identify the underlying gene mutations causing non-syndromic arRP. RESULTS: Our study revealed disease-causing mutations in known arRP genes for 10 of the 13 families studied (76.9%). These mutations included two-frameshift insertion/deletion in CRB1 and ABCA4, one splicing mutation in PDE6B, four missense mutations in RP1, CRB1, PANK2 and IFT140, as well as three stop codon mutations in RDH12, PRCD, and C2orf71. Three remaining families harbored no mutation in previously known RP genes. Of the 10 diseases causing mutations identified among the investigated Iranian patients with non-syndromic arRP, eight variants had not been reported previously. We confirmed segregation of all 10 mutations with disease phenotypes in our studied population. CONCLUSION: This study supports the genetic heterogeneity of non-syndromic arRP in Iranian patients, and provides an opportunity to show the effectiveness of WES in the identification of pathogenic mutations among patients with non-syndromic arRP born to consanguineous parents.
BACKGROUND:Non-syndromic autosomal recessive Retinitis Pigmentosa (arRP) is a highly heterogeneous genetic visual disorder with a large number of causative genes. We aimed to determine the power of Whole Exome Sequencing (WES) in the identification of the genes responsible for non-syndromic arRP among Iranian patients. METHODS: We used WES, followed by the Sanger sequencing to identify the underlying gene mutations causing non-syndromic arRP. RESULTS: Our study revealed disease-causing mutations in known arRP genes for 10 of the 13 families studied (76.9%). These mutations included two-frameshift insertion/deletion in CRB1 and ABCA4, one splicing mutation in PDE6B, four missense mutations in RP1, CRB1, PANK2 and IFT140, as well as three stop codon mutations in RDH12, PRCD, and C2orf71. Three remaining families harbored no mutation in previously known RP genes. Of the 10 diseases causing mutations identified among the investigated Iranian patients with non-syndromic arRP, eight variants had not been reported previously. We confirmed segregation of all 10 mutations with disease phenotypes in our studied population. CONCLUSION: This study supports the genetic heterogeneity of non-syndromic arRP in Iranian patients, and provides an opportunity to show the effectiveness of WES in the identification of pathogenic mutations among patients with non-syndromic arRP born to consanguineous parents.
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