Novel genetic causes for cerebral visual impairment.

TitleNovel genetic causes for cerebral visual impairment.
Publication TypeJournal Article
Year of Publication2016
AuthorsBosch, DGM, F Boonstra, N, de Leeuw, N, Pfundt, R, Nillesen, WM, de Ligt, J, Gilissen, C, Jhangiani, S, Lupski, JR, Cremers, FPM, de Vries, BBA
JournalEur J Hum Genet
Date Published2016 May
KeywordsAdolescent, Blindness, Cortical, Child, Child, Preschool, Female, Genetic Loci, Humans, Male, Polymorphism, Single Nucleotide, Young Adult

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.

Alternate JournalEur J Hum Genet
PubMed ID26350515
PubMed Central IDPMC4930090
Grant ListU54 HG006542 / HG / NHGRI NIH HHS / United States
U54HG006542 / HG / NHGRI NIH HHS / United States

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