Abstract
Cerebral visual impairment (CVI) is a major cause of low vision in children due to impairment in projection and/or interpretation of the visual input in the brain. Although acquired causes for CVI are well known, genetic causes underlying CVI are largely unidentified. DNAs of 25 patients with CVI and intellectual disability, but without acquired (eg, perinatal) damage, were investigated by whole-exome sequencing. The data were analyzed for de novo, autosomal-recessive, and X-linked variants, and subsequently classified into known, candidate, or unlikely to be associated with CVI. This classification was based on the Online Mendelian Inheritance in Man database, literature reports, variant characteristics, and functional relevance of the gene. After classification, variants in four genes known to be associated with CVI (AHDC1, NGLY1, NR2F1, PGAP1) in 5 patients (20%) were identified, establishing a conclusive genetic diagnosis for CVI. In addition, in 11 patients (44%) with CVI, variants in one or more candidate genes were identified (ACP6, AMOT, ARHGEF10L, ATP6V1A, DCAF6, DLG4, GABRB2, GRIN1, GRIN2B, KCNQ3, KCTD19, RERE, SLC1A1, SLC25A16, SLC35A2, SOX5, UFSP2, UHMK1, ZFP30). Our findings show that diverse genetic causes underlie CVI, some of which will provide insight into the biology underlying this disease process.
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Acknowledgements
We are grateful to the individuals involved and their families for their support and cooperation. We thank the technical ophthalmological assistant and orthoptists for their assistance during the ophthalmological examinations, with special thanks to Piet Rison. We thank Lisenka Vissers for the helpful discussions and support. This work has been supported by grants from Stichting ODAS (to FNB and FPMC), Vereniging Bartiméus-Sonneheerdt (5781251 to FNB and FPMC), and the Dutch Organisation for Health Research and Development (ZON-MW grants 917-86-319 and 912-12-109 to BBAdV). Additionally, this study was accomplished in part through the Center for Mendelian Genomics research effort funded by the National Institutes of Health and supported by the National Human Genome Research Institute grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics.
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Bosch, D., Boonstra, F., de Leeuw, N. et al. Novel genetic causes for cerebral visual impairment. Eur J Hum Genet 24, 660–665 (2016). https://doi.org/10.1038/ejhg.2015.186
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DOI: https://doi.org/10.1038/ejhg.2015.186
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