title: Whole Exome Sequencing Reveals Mutations in Known Retinal Disease Genes in 33 out of 68 Israeli Families with Inherited Retinopathies.
abstract: Whole exome sequencing (WES) is a powerful technique for identifying sequence changes in the human genome. The goal of this study was to delineate the genetic defects in patients with inherited retinal diseases (IRDs) using WES. WES was performed on 90 patient DNA samples from 68 families and 226 known genes for IRDs were analyzed. Sanger sequencing was used to validate potential pathogenic variants that were also subjected to segregation analysis in families. Thirty-three causative mutations (19 novel and 14 known) in 25 genes were identified in 33 of the 68 families. The vast majority of mutations (30 out of 33) have not been reported in the Israeli and the Palestinian populations. Nine out of the 33 mutations were detected in additional families from the same ethnic population, suggesting a founder effect. In two families, identified phenotypes were different from the previously reported clinical findings associated with the causative gene. This is the largest genetic analysis of IRDs in the Israeli and Palestinian populations to date. We also demonstrate that WES is a powerful tool for rapid analysis of known disease genes in large patient cohorts.
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Avigail
authors: A
authors: Beryozkin
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Elia
authors: E
authors: Shevah
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Adva
authors: A
authors: Kimchi
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Liliana
authors: L
authors: Mizrahi-Meissonnier
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Samer
authors: S
authors: Khateb
authors: Neurobiology-Neurodegeneration &Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Rinki
authors: R
authors: Ratnapriya
authors: Neurobiology-Neurodegeneration &Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.|Molecular Biology Center, Interdisciplinary Research Institute on Bio-Nano Sciences, Babes-Bolyai-University, Cluj-Napoca, 400271, Romania.
authors: Csilla H
authors: CH
authors: Lazar
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Anat
authors: A
authors: Blumenfeld
authors: Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors: Tamar
authors: T
authors: Ben-Yosef
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Yitzhak
authors: Y
authors: Hemo
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Jacob
authors: J
authors: Pe'er
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Eduard
authors: E
authors: Averbuch
authors: Human Genetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Michal
authors: M
authors: Sagi
authors: Neurobiology-Neurodegeneration &Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Alexis
authors: A
authors: Boleda
authors: Neurobiology-Neurodegeneration &Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Linn
authors: L
authors: Gieser
authors: Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Abraham
authors: A
authors: Zlotogorski
authors: Institute of Human Genetics, The Galilee Medical Center, Naharia, Israel; The Galilee Faculty of Medicine, Bar-Ilan, Israel.
authors: Tzipora
authors: T
authors: Falik-Zaccai
authors: Ha'emek hospital, Afula, Israel.
authors: Ola
authors: O
authors: Alimi-Kasem
authors: Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Samuel G
authors: SG
authors: Jacobson
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Itay
authors: I
authors: Chowers
authors: Neurobiology-Neurodegeneration &Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Anand
authors: A
authors: Swaroop
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Eyal
authors: E
authors: Banin
authors: Departments of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Dror
authors: D
authors: Sharon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018912:Arabs / Q000706:statistics & numerical data; D002874:Chromosome Mapping / Q000379:methods; D059472:Exome / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007557:Israel / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D012164:Retinal Diseases / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D005819:Genetic Markers