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Nicola Bedoni, Konstantinos Nikopoulos, Pietro Farinelli, Beryl Royer-Bertrand, Sara Balzano, Sten Andreasson, Miltiadis K Tsilimbaris, Chrysanthi Tsika, Stella Blazaki, Carlo Rivolta; Whole exome screening and identification of novel variants in a cohort of 28 Greek and Swedish families with cone-rod dystrophy.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):671.
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© ARVO (1962-2015); The Authors (2016-present)
The wide genetic heterogeneity of cone-rod dystrophies (CRDs) poses a challenge for patients’ clinical and molecular diagnosis. To date, more than 30 genes have been associated with non-syndromic CRDs, accounting roughly for ~40% of all reported cases. We screened a cohort of 28 probands from Greek and Swedish families using whole exome sequencing (WES) with the purpose of assessing their genetic landscape.
Following clinical evaluation, 28 probands were analyzed by means of WES using the Illumina HiSeq2500 platform. An in-house in silico pipeline was used for data processing. Briefly, prioritization of disease causing variants was achieved on the basis of: (1) prevalence in healthy human populations, (2) predicted annotations, (3) expression of the affected gene in the retina, and (4) pedigree co-segregation analyses within the probands’ pedigree.
In our cohort, WES revealed putative disease-causing variants in eight known CRD genes (ABCA4, RPGRIP1, CDHR1, CRX, PRPH2, RIMS1, RAB28, and PROM1), affecting patients from 13 families. In two other families, mutations in HGSNAT and ARL6, usually associated with retinitis pigmentosa, prompted us to reassess their clinical evaluation. The remaining 13 families are presently still unsolved and will be subject to further analyses (e.g. screening of patient cohorts for candidate variants, or whole genome sequencing to detect deep intronic variants or structural abnormalities).
We could identify causative mutations in ~45% of all cases. Our findings provide further insight into the genetic variations behind cone-rod dystrophy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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