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Michelle Grunin, Liran Tiosano, Tareq Jaouni, Shira Hagbi-Levi, Edward Averbukh, Dror Sharon, Itay Chowers; Genetic Analysis of Adult-Onset Foveomacular Vitelliform Dystrophy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1263. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
A minority of patients with adult-onset foveomacular vitelliform dystrophy (AFVD) carry mutations in the PRPH2, IMPG1/2 or BEST1 genes. We have previously associated this phenotype with an HTRA1 single nucleotide polymorphism (SNP). Exon 3 of PRPH2 gene is highly polymorphic, and variants in this region were suggested as candidates for association with AFVD. We aim to assess for genetic variants underlying this phenotype in the PRPH2 gene.
A single center cohort including 52 consecutive patients with a clinical diagnosis of sporadic AFVD was evaluated. Factors previously associated with acquired vitelliform lesions in adults were excluded. A cohort of 91 unaffected age-matched controls from the same referral center served as controls. PCR and Sanger sequencing was performed for PRPH2, IMPG1/2, and BEST1 genes, for both patients and controls. Investigations of minor alleles for SNPs in PRPH2 was performed, examined using GAP from the Staden package (http://staden.sourceforge.net/) and Chromas (Technelysium, http://technelysium.com.au/) and compared to HapMap and Exome Variant Server (EVS) data
No mutations were found in BEST1, IMPG1, IMPG2, or PRPH2 in any of the patients or controls tested. A high frequency and percentage of minor alleles of five SNPs found in exon 3 of PRPH2 was found in AFVD Israeli patients along with the controls, and was not found in the HapMap or EVS populations. One SNP, rs835, showed a trend (P=0.10) towards association with AFVD in the Israeli population. Power calculation suggested that our sample size was sufficient (80%) to rule out significance toward any SNP that did not have an odds ratio above 2.5.
These results suggest that mutations in BEST1, IMPG1/2, and mutations or genetic variants in PRPH2 do not compose a major genetic risk factor for AFVD. In the Israeli population, a higher percentage of minor allele frequencies in the exon 3 of PRPH2 are present compared with other populations. Genetic or other factors which underlie the majority of the sporadic AFVD phenotype remain to be identified.
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