Impact of whole exome sequencing among Iranian patients with autosomal recessive retinitis pigmentosa.
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.


CONCLUSIONS
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.
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Maryam
M
Beheshtian
Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran, Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran.
Samira
S
Saee Rad
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Mojgan
M
Babanejad
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Marzieh
M
Mohseni
Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran.
Hassan
H
Hashemi
Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran.
Arash
A
Eshghabadi
Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran.
Fedra
F
Hajizadeh
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.
Mohammad Reza
MR
Akbari
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Kimia
K
Kahrizi
Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran.
Mohammad
M
Riazi Esfahani
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. hnajm12@yahoo.com.
Hossein
H
Najmabadi
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D059472:Exome / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D007492:Iran; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000145:classification* / Q000235:genetics*; D055815:Young Adult
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517431:PDE6B protein, human