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A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC)
Author(s) -
Sharon Dror,
BenYosef Tamar,
GoldenbergCohen Nitza,
Pras Eran,
Gradstein Libe,
Soudry Shiri,
Mezer Eedy,
Zur Dinah,
Abbasi Anan H.,
Zeitz Christina,
Cremers Frans P. M.,
Khan Muhammad I.,
Levy Jaime,
Rotenstreich Ygal,
Birk Ohad S.,
Ehrenberg Miriam,
Leibu Rina,
Newman Hadas,
Shomron Noam,
Banin Eyal,
Perlman Ido
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23903
Subject(s) - abca4 , retinitis pigmentosa , stargardt disease , biology , genetics , retinal degeneration , disease , genetic testing , retinal , genetic heterogeneity , cohort , phenotype , pathology , gene , medicine , biochemistry
Inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptors. These diseases show marked phenotypic and genetic heterogeneity. The Israeli IRD consortium (IIRDC) was established in 2013 with the goal of performing clinical and genetic mapping of the majority of Israeli IRD patients. To date, we recruited 2,420 families including 3,413 individuals with IRDs. On the basis of our estimation, these patients represent approximately 40% of Israeli IRD patients. To the best of our knowledge, this is, by far, the largest reported IRD cohort, and one of the first studies addressing the genetic analysis of IRD patients on a nationwide scale. The most common inheritance pattern in our cohort is autosomal recessive (60% of families). The most common retinal phenotype is retinitis pigmentosa (43%), followed by Stargardt disease and cone/cone–rod dystrophy. We identified the cause of disease in 56% of the families. Overall, 605 distinct mutations were identified, of which 12% represent prevalent founder mutations. The most frequently mutated genes were ABCA4, USH2A, FAM161A, CNGA3 , and EYS . The results of this study have important implications for molecular diagnosis, genetic screening, and counseling, as well as for the development of new therapeutic strategies for retinal diseases.