Dror Sharon1, Tamar Ben-Yosef2, Eran Pras3,4, Nitza Goldenberg-Cohen2,5,6, Libe Gradstein7, Noam Shomron4, Ohad Birk8,9, Miriam Ehrenberg10, Jaime Levy1, Eedy Mezer2,11, Shiri Soudry11, Ygal Rotenstreich4,12, Hadas Newman4,13, Rina Leibu11, Eyal Banin1, Ido Perlman2,13. 1. Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem. 2. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa. 3. Department of Ophthalmology, Assaf-Harofeh Medical Center, Zerifin. 4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv. 5. Department of Ophthalmology, Bnai Zion Medical Center, Haifa. 6. The Krieger Eye Research Laboratory, Petah Tikva. 7. Department of Ophthalmology, Soroka Medical Center and Clalit Health Services, Faculty of Health Sciences, Ben-Gurion University, Beer Sheva. 8. The Morris Kahn Laboratory of Human Genetics at the National Institute of Biotechnology in the Negev, Ben-Gurion University, Beer Sheva. 9. Genetics Institute, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University, Beer Sheva. 10. Ophthalmology Unit, Schneider Children's Medical Center in Israel, Petah Tikva. 11. Department of Ophthalmology, Rambam Healthcare Campus, Haifa. 12. The Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer. 13. Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv.
Abstract
INTRODUCTION: The sense of vision is highly important for humans and its loss markedly affects function and quality of life. Many inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptor cells. These diseases show clinical and genetic heterogeneity. AIMS: The Israeli IRD consortium (IIRDC) was established with the goal of performing clinical and genetic mapping of IRDs in the Israeli population. METHODS: Clinical evaluation is carried out at electroretinography (ERG) centers and ophthalmology departments, where the patients undergo a comprehensive eye exam, including testing of visual acuity, refractive error, imaging techniques and ERG tests. Genetic analysis is performed using Sanger sequencing, analysis of founder mutations, and whole exome sequencing. RESULTS: We recruited over 2,000 families including more than 3,000 individuals with IRDs. The most common inheritance pattern is autosomal recessive (65% of families). The most common retinal phenotype is retinitis pigmentosa (RP- 45% of families), followed by cone/cone-rod dystrophy, Stargardt Disease and Usher syndrome. We identified the cause of disease in 51% of families, mainly due to mutations in ABCA4, USH2A, FAM161A, CNGA3, and EYS. IIRDC researchers were involved in the identification of 16 novel IRD genes. In parallel, IIRDC members are involved in the development of therapeutic modalities for these currently incurable diseases. CONCLUSIONS: IIRDC works in close collaborative efforts aiming to continue and recruit for the genotype - phenotype study from the vast majority of Israeli IRD families, to identify all disease-causing mutations, and to tailor therapeutic interventions to each IRD patient.
INTRODUCTION: The sense of vision is highly important for humans and its loss markedly affects function and quality of life. Many inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptor cells. These diseases show clinical and genetic heterogeneity. AIMS: The Israeli IRD consortium (IIRDC) was established with the goal of performing clinical and genetic mapping of IRDs in the Israeli population. METHODS: Clinical evaluation is carried out at electroretinography (ERG) centers and ophthalmology departments, where the patients undergo a comprehensive eye exam, including testing of visual acuity, refractive error, imaging techniques and ERG tests. Genetic analysis is performed using Sanger sequencing, analysis of founder mutations, and whole exome sequencing. RESULTS: We recruited over 2,000 families including more than 3,000 individuals with IRDs. The most common inheritance pattern is autosomal recessive (65% of families). The most common retinal phenotype is retinitis pigmentosa (RP- 45% of families), followed by cone/cone-rod dystrophy, Stargardt Disease and Usher syndrome. We identified the cause of disease in 51% of families, mainly due to mutations in ABCA4, USH2A, FAM161A, CNGA3, and EYS. IIRDC researchers were involved in the identification of 16 novel IRD genes. In parallel, IIRDC members are involved in the development of therapeutic modalities for these currently incurable diseases. CONCLUSIONS: IIRDC works in close collaborative efforts aiming to continue and recruit for the genotype - phenotype study from the vast majority of Israeli IRD families, to identify all disease-causing mutations, and to tailor therapeutic interventions to each IRD patient.