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Qingjiong Zhang, Xueshan Xiao, Shiqiang Li, Xiaoyun Jia, Xiangming Guo; Reinspection of FEVR based on exome sequencing: a common disease with extremely variable phenotypes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1237.
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© ARVO (1962-2015); The Authors (2016-present)
Familial exudative vitreoretinopathy (FEVR) has been described as a rare hereditary disease with variable phenotypes based on study of families with typical signs. This study is to explore to what extent such variable phenotypes might be and the presumed prevalence of FEVR based on frequency of potential pathogenic mutations (PPM).
A cohort of 2429 Chinese probands with different forms of hereditary retinal diseases (HRD) other than FEVR were collected from our clinic and their genomic DNA was analyzed by whole exome sequencing. Variations in genes know to associated with FEVR, such as FZD4, LRP,TSPAN12, KIF11, NDP, etc, were collected and analyzed by multiple informatics analysis in order to identify PPM. Reexamination of clinical data as well as probands and available family members was carried out to identify key signs of FEVR in these patients with PPM but with other forms of HRD. Data from controls and online database were used to filter out unlikely PPM.
Totally, PPM in FEVR-related genes were detected in about 6.7% of the 2429 probands. About half of the mutations were previously reported to be causative for FEVR. Comparing the PPM with data from controls and online database, about half of the PPM (mostly frequently reported ones) might not be causative, which has been further supported by reexamination of the patients and controls. For the rest half of the PPM, clinical data and fluorescein angiography demonstrated typical signs of FEVR although they were clinically considered as other forms of HRD, such as early-onset high myopia, cone-rod dystrophy, juvenile retinal detachment, macular degeneration, macular hypoplasia, glaucoma, etc. Taking into account of the high prevalence of the HRD, the presumed prevalence of FEVR might be more than 1 in 2000 based on the frequency of PPM detected.
The results not only greatly expand the phenotypic variation of FEVR based on genotypes but also indicate FEVR as a common disease. Recognizing signs suggestive for FEVR may facilitate the clinical diagnosis and management. Gene diagnosis based on systematic genetic analysis may reveal unexpected molecular basis for atypical diseases while provide useful information for clarifying false positive results.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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